Lower FT3 Levels Research Articles

Thyrotropin N-glycosylation and Glycan Composition in Severe Primary Hypothyroidism.

ContextIn severe primary hypothyroidism (sPH), the serum thyrotropin (TSH) levels are elevated with an increased degree of sialylation. The circulating TSH comprises 2 different TSH glycoforms: TSHdi with 2 and TSHtri with 3 N-glycans and methods have developed to determine their contents of anionic monosaccharides (AMS), that is, sialic acid (SA) and sulfonated N-acetylglactosamine (SU) residues.ObjectiveCharacterize N-glycosylation and glycan composition of circulating TSH molecules and determine the effects during levothyroxine treatment in patients with sPH.MethodsSerum samples were obtained from 25 patients with sPH, from 159 euthyroid individuals, and from 12 women during treatment with levothyroxine for sPH. Degrees of N-glycosylation and concentrations of TSHdi and TSHtri as well as their contents of AMS, SA, and SU residues were determined.ResultsThe circulating TSH molecules in sPH patients had lower degrees of N-glycosylation, higher degrees of sialylation, and lower degrees of sulfonation than in euthyroid individuals. Levothyroxin restored sialylation and sulfonation of the glycans already at low free thyroxine (FT4) levels, while degree of N-glycosylation was not restored until the FT4 levels were normal.ConclusionsThe majority of TSH molecules in severe primary hypothyroidism were less N- glycosylated, more sialylated, and less sulfonated compared with euthyroid individuals. This glycan pattern favors a prolonged half-life in the circulation combined with lower in vitro biopotency at the target cells. During levothyroxine treatment of sPH patients, the sialylation and sulfonation of glycans were restored already at low FT4 levels, while N-glycosylation of TSH was not restored until the FT4 levels were normal.

Prognostic value of free triiodothyronine and N-terminal pro-B-type natriuretic peptide for patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study

BackgroundAltered thyroid function and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) are prognostic factors in acute myocardial infarction (AMI). The study aims to investigate whether free triiodothyronine (fT3) and NT-proBNP are prognostic factors for long-term outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI).MethodsThis was an observational, prospective, single-center study of consecutive patients enrolled at Fuwai Hospital between January, 2013 and December, 2013. The patients were divided into two groups according to fT3 levels: low fT3 (<2.5 pg/mL) and normal fT3 (2.50–4.09 pg/mL). The primary outcome of this study was the incidence of major adverse cardiovascular events (MACEs).ResultsThere were 252 patients with low fT3 and 561 patients with normal fT3. After >2 years of follow-up, patients with low fT3 levels had higher rates of MACEs than those with normal fT3 (27.0% vs. 7.8%, P<0.001). Univariable Cox proportional hazards regression analyses showed that NT-proBNP >802.7 pg/mL [hazard ratio (HR) =5.063, 95% confidence interval (CI): 3.176–8.071, P<0.001] and fT3 <2.5 pg/mL (HR =3.867, 95% CI: 2.646–5.651, P<0.001) were the strongest predictors of MACEs. After adjustment for traditional risk predictors, fT3 <2.5 pg/mL (HR =2.570, 95% CI: 1.653–3.993, P<0.001) was one of the most important independent predictors of MACEs. Patients with NT-proBNP ≤802.7 pg/mL and fT3 ≥2.5 pg/mL had the best prognosis, while patients with NT-proBNP >802.7 pg/mL and fT3 <2.5 pg/mL had the worst outcomes (P<0.001).ConclusionsLow fT3 is a strong predictor of poor prognosis after AMI. The fT3+NT-proBNP combination might be a valuable predictor of the long-term outcomes of PCI after AMI.

Prognostic role of hypothyroidism and low free-triiodothyronine levels in patients hospitalized with acute heart failure.

Low thyroid function has been widely recognized as a potential cause of heart failure (HF), but the evidence about a possible association with in-hospital, all-cause mortality in patients with acute HF (AHF) is not consistent. This study sought to investigate the prevalence and prognostic role of hypothyroidism, overt and subclinical, and of low free-triiodothyronine (fT3) levels in patients hospitalized with AHF. We retrospectively analyzed consecutive 1018 patients who were hospitalized for AHF in a single academic medical center [Fondazione Policlinico A.Gemelli IRCCS, Rome, Italy] between January 1st 2016, and December 31st 2018. Patients were divided into three groups: normal thyroid function (n = 798), subclinical hypothyroidism (n = 105), and overt hypothyroidism (n = 115). The outcome was in-hospital, all-cause mortality. Patients were 81years of age, 55% were females and nearly two-thirds of the patients were on New York Heart Association functional class III. The three most common cardiovascular comorbidities were coronary artery disease, hypertension, and atrial fibrillation with no differences across the three groups. Overall, 138 patients (14%) died during the hospital stay. The mortality rate was 27% among patients with overt hypothyroid, 17% among those with subclinical hypothyroidism, and 11% among euthyroid patients (p < 0.001). At a multivariate Cox regression model, overt hypothyroidism (HR 2.1, 95% CI 1.4-3.2) and fT3 levels < 1.8pg/mL (HR 3.4, 95% CI 2.3-5.1) were associated with an increased likelihood of in-hospital death. No association was found with subclinical hypothyroidism. Among patients hospitalized with AHF, overt hypothyroidism and low fT3 levels are independent predictors of all-cause mortality during the hospital stay.

Association between thyroid function and risk of gestational diabetes mellitus in assisted pregnancies: A retrospective cohort study

AimsTo explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies. MethodsWe screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI). ResultsThe prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (ORQ2 = 1.512, 95% confidence interval [CI] 1.073–2.132, p = 0.018; ORQ1 = 1.620, 95% CI 1.161–2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068–2.028, p = 0.018). Higher TSH (aORQ5 = 2.882, 95% CI 1.919–6.975, p = 0.019) or lower FT4 (aORQ1 = 3.156, 95% CI 1.088–9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients. ConclusionTPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies.

Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS)

ABSTRACT Introduction: To determine age and sex-specific thyrotropin (TSH) and free thyroxine (FT4) reference ranges according to body mass index (BMI) categories. Methods: With regards to the National Academy of Clinical Biochemistry (NACB) criteria, a total of 2818 individuals from the Tehran Thyroid Study population was selected and categorized in three BMI groups. Results: TSH levels did not differ significantly between BMI groups (p = .054). Females had statistically higher TSH levels than males in all BMI categories (p < .001). According to age-specific analyses, the youngest category (20–29 years) had the highest median values of serum TSH in all BMI groups. With increasing BMI, the 2.5th percentile of TSH remained approximately unchanged and the 97.5th percentile showed an increasing pattern. FT4 level was significantly higher in the normal weight group compared to obese individuals (p < .001); females had significantly lower FT4 levels than males in normal weight and obese groups (p < .001). According to age categories, the youngest group (20–29 years) had higher levels of FT4 than the elderly group in all BMI categories. A decreasing pattern in both 2.5th and 97.5th percentiles of FT4 was observed along with increasing BMI. Conclusions: Compared to the normal weight population, obese individuals have slightly lower FT4 concentrations accompanied by similar TSH levels. With increasing BMI, upper limits of TSH and FT4 show increasing and decreasing patterns, respectively.

Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case-Control Study.

ObjectiveThe aim of this study was to assess the prevalence of thyroid autoimmunity in T2DM with NAFLD, furthermore explore the relationship between elevated TPOAb titer and the severity of NAFLD.MethodsA total of 400 patients with T2DM were divided into two groups according to NAFLD. Thyroid function and other metabolic indicators were measured.ResultsThere were more TPOAb-positive patients in both groups, and the prevalence of TPOAb positive was significantly different in two groups (17% vs 6.9%, p< 0.01). FT4 was significantly lower in patients with T2DM with NAFLD (median FT4 0.89 vs 1.08, p < 0.001), while TSH was increased (median TSH 2.85 vs 2.28, p < 0.05). In patients with T2DM with NAFLD, the proportion of women in the thyroid autoimmune-positive group was significantly higher than the negative (71.1% vs 46%, p < 0.01). Similarly, thyroid autoimmune-positive T2DM and NAFLD patients had lower FT4 levels (median FT4 0.59 vs 0.92, p < 0.001), higher TSH levels (median TSH 3.65 vs 2.67, p < 0.001), and much higher TPOAb/TGAb (median TPOAb/TGAb 6.8 vs 1.46, p < 0.001). The increase of TPOAb was significantly correlated with the severity of fatty liver. HbA1c, TC, TG, TSH, TPOAb/TGAb and severity of fatty liver were risk factors of thyroid autoimmunity.ConclusionAutoimmune thyroid disease is more common in patients with T2DM complicated with NAFLD. Elevated TPOAb titer is closely related to fatty liver, suggesting that elevated TPOAb titer is a predictor of autoimmune development in T2DM with NAFLD.

Thyroid Hormones, Silencing Mediator for Retinoid and Thyroid Receptors and Prognosis in Primary Breast Cancer.

Silencing mediator of retinoid and thyroid receptors (SMRT) is a nuclear corepressor in thyroid and estrogen hormones pathways. The aim was to evaluate SMRT expression in relation to thyroid hormone levels and prognostic markers in breast cancer (BC). Serum and tumor tissues were obtained from 36 patients with benign breast disease (BBD) and 79 BC patients. SMRT expression was determined by immunohistochemistry. Free-triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured in serum. Higher FT4, lower FT3/FT4 ratio and higher expression of SMRT were found in BC compared to BBD (for all p<0.001). In BC, increased SMRT expression was associated with lower FT3 (p=0.028), higher tumor grade (p=0.031), increased KI67 proliferation index (p=0.015), higher risk of recurrence (p=0.014) and shorter disease-free survival (p=0.006). In multivariate analysis, SMRT overexpression and below-median levels of TSH were independent prognostic factors in BC. Elevated FT4 and decreased FT3/FT4 in BC patients suggest a role for thyroid hormones in malignant transformation. SMRT tumor overexpression is associated with lower FT3 levels, tumor proliferative activity and an aggressive clinical course.

Abnormal and Euthyroid Ranges of Thyroid Hormones in Serum and Liver Cancer Mortality: A Cohort Study.

This study aimed to evaluate the relationship of serum thyrotropin (TSH) and thyroid hormone concentration with liver cancer mortality. A cohort of 517,996 Korean adults, who did not have liver cancer at baseline and attended a health screening including free thyroxine (FT4) and TSH, were followed for up to 16 years. High and low TSH and FT4 were defined as those above the upper bound of reference interval and those below the lower bound of reference interval of their corresponding reference intervals, respectively. Mortality information was ascertained through National Death Records. The adjusted HR (aHR) with 95% confidence interval (CI) were estimated using a Cox proportional hazard model. During a median follow-up of 8.1 years, 376 deaths from liver cancer were identified. Subjects with low FT4 levels were associated with an elevated risk of liver cancer mortality with a corresponding multivariable aHR 2.25 (95% CI: 1.62-3.12) compared with those with normal FT4 levels. Within the euthyroid range, there was also a dose-dependent inverse relationship between FT4 level and liver cancer mortality (P < 0.001). Levels of TSH and free T3 had no significant association with liver cancer mortality. The risk of liver cancer mortality increased as FT4 level decreased, both within the normal and abnormal ranges of thyroid function. Thyroid function within the abnormal and normal ranges might affect liver cancer mortality. Further study is warranted to elucidate the role of thyroid hormone in development of liver cancer including the underlying biological mechanism.

The significance of high thyroxine in hospitalized patients with low thyroid-stimulating hormone

There is scarce data about the interpretation of high thyroid hormone levels in hospitalized patients. We wished to investigate the significance of high thyroxine (T4) in hospitalized patients with low TSH. We conducted a retrospective study of data from patients in nonsurgical departments. Three groups of random patients with low TSH were defined and compared: 123 patients with only high FT4 levels (T4 group), 82 with high FT3 levels with or without high FT4 level (T3 group), and 119 with low FT3 and FT4 level in the lower half of the norm and below (NTIS group). The primary cause of admission in the T4 and NTIS groups was infectious disease, 20.3% and 40.3%, respectively; while in the T3 group it was cardiovascular disease (31.7%). The T4 group but not T3 group had epidemiological and clinical characteristics similar to the NTIS group. The T4 group had a significant correlation between increased CRP levels and decreased FT3 (r = 0.366, p < 0.001) similar to the NTIS group. The T3 group had a borderline correlation between increased FT3 and FT4 levels (r = 0.208, p = 0.061) but the T4 group did not. The combination of low TSH and high FT4 levels in hospitalized patient is usually caused by nonthyroidal illness combined with drug effects. This thyroid function disturbance is common in hospitalized patients and if the FT3 level is below the middle of the norm, treatment is probably unnecessary.

Relationship Between Thyroid Hormones and Left Ventricular Mass in Peritoneal Dialysis Patients.

Introduction. Non-thyroidal illness is prevalent in patients with advanced stages of chronic kidney disease and could be considered as a risk factor for cardiovascular mortality; this relation is partially explained by malnutrition and the concomitant condition of high inflammation. This study is designed to investigate the relationship between left ventricular mass and thyroid hormone abnormalities and evaluate this relationship after adjustment of inflammatory factors and nutritional status in peritoneal dialysis patients. Methods. A total of 71 patients undergoing maintenance peritoneal dialysis were included. Serum concentration of total and free triiodothyronine (fT3), total and free thyroxine (fT4), and TSH were measured. LV mass index and the structural properties of heart including LVEDD, LVESD, PWD, and EF were assessed by transthoracic echocardiography. The Surrogates of Inflammation, including IL-6, albumin, and hs-CRP were measured. The nutritional status of patients was assessed by one point SGA scoring and biochemical data. The relation between thyroid hormones and echocardiographic variables, inflammatory and nutritional markers was determined. Results. LVMI was significantly higher in the group with lower fT3 levels. Linear regression analyses showed statistically significant univariate association between fT3, tT3, and tT4; and LVMI. In multiple linear regression analysis adjusted for albumin, hs-CRP, IL- 6, and ferritin; only fT3 level had a meaningful negative correlation (P < .05) with LVMI, free T3 level was positively correlated with rGFR (P < .05, c = 0.39) and KT/V (P < .05, c = 0.27). Conclusion. Low fT3 level was negatively and significantly associated with LVML even after adjustments for known risk factors in peritoneal dialysis patients.

Low free triiodothyronine levels are associated with risk of frailty in older adults with type 2 diabetes mellitus.

With aging populations around the world, frailty is becoming more prevalent increasing the need to early identify those at risk of frailty. The association between thyroid hormone levels and frailty in subjects with type 2 diabetes mellitus (T2DM) remains unclear. The objective of the study was to evaluate the relationship between thyroid hormone concentrations and frailty in older adults with T2DM. A total of 240 older adults with T2DM were divided into three groups according to the frailty phenotype criteria: robust group (n=94), pre-frail (n=110) and frail group (n=36). Concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D3 [25(OH) D3], highly sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were determined. Handgrip strength was measured using a Jamar hand dynamometer. Physical function was assessed by gait speed and the timed go and up (TUG) test. Logistic regression analysis was performed to evaluate the association between FT3 and frailty. The FT3 level was the lowest among frail people (2.56±0.42pg/mL), followed by pre-frail participants (2.73±0.38pg/mL), with the highest among the robust subjects (2.83±0.43pg/mL). FT3 level was positively correlated with handgrip strength and gait speed (R=0.313, P<0.001; R=0.250, P<0.001, respectively), while negatively correlated with TUG time (R=-0.276, P<0.001). After adjusting for age, sex, TSH, 25(OH) D3 and estimate glomerular filtration rate (eGFR), logistic regression showed that low FT3 was significantly associated with an increased risk of frailty (odds ratio (OR): 4.53; 95% confidence interval (CI): 1.89-10.83; P=0.001). Low levels of FT3 were associated with an increased risk of frailty in older adults with T2DM. Measuring FT3 might be useful for identifying those at high risk of frailty.

Importance of Thyroid Hormone level and Genetic Variations in Deiodinases for Patients after Acute Myocardial Infarction: A Longitudinal Observational Study

This study aimed to examine the influence of thyroid hormone (TH) levels and genetic polymorphisms of deiodinases on long-term outcomes after acute myocardial infarction (AMI). In total, 290 patients who have experienced AMI were evaluated for demographic, clinical characteristics, risk factors, TH and NT-pro-BNP. Polymorphisms of TH related genes were included deiodinase 1 (DIO1) (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), deiodinase 2 (DIO2) (rs225015-G/A, rs225014-T/C) and deiodinase 3 (DIO3) (rs945006-T/G). Both all-cause and cardiac mortality was considered key outcomes. Cox regression model showed that NT-pro-BNP (HR = 2.11; 95% CI = 1.18– 3.78; p = 0.012), the first quartile of fT3, and DIO1 gene rs12095080 were independent predictors of cardiac-related mortality (HR = 1.74; 95% CI = 1.04–2.91; p = 0.034). The DIO1 gene rs12095080 AG genotype (OR = 3.97; 95% CI = 1.45–10.89; p = 0.005) increased the risk for cardiac mortality. Lower fT3 levels and the DIO1 gene rs12095080 are both associated with cardiac-related mortality after AMI.

Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study.

BackgroundHypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function.MethodsThyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status.ResultsCross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint.ConclusionsPatients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

Iron Deficiency, a Risk Factor for Thyroid Autoimmunity During Second Trimester of Pregnancy in China

Objective: Previous studies have reported an association between iron deficiency (ID) and increased thyroid peroxidase antibody (TPO-Ab) during early pregnancy. The objective of this study was to explore the relationship between ID and thyroid dysfunction, as well as thyroid autoantibodies, during the second trimester of pregnancy. Methods: A total of 1,592 pregnant women (13 to 28 weeks gestation) were enrolled in this cross-sectional study. According to serum ferritin (SF) concentrations, they were divided into ID (SF <20 μg/L) or non-ID (SF ≥20 μg/L) groups. Logistic regression analysis was used to evaluate the association between ID and subclinical hypothyroidism (thyroid-stimulating hormone [TSH] >4.0 mIU/L and free thyroxine [FT4] within the reference range) and thyroid autoimmunity. Results: The prevalence of ID was 23.43% (373/1,592). Compared with the non-ID group, the ID group had lower FT4 levels (13.94 pmol/L [8.91 to 29.82 pmol/L] versus 14.63 pmol/L [8.22 to 47.24 pmol/L]; P<.001]) and higher TSH levels (1.85 mIU/L [0.01 to 7.84 mIU/L] versus 1.69 mIU/L [0.01 to 10.2 mIU/L]; P<.05). Logistic regression analysis confirmed ID as a risk factor for increased thyroglobulin antibody (TG-Ab) (odds ratio 1.974; 95% confidence interval 1.065, 3.657; P<.05), but not for subclinical hypothyroidism or increased TPO-Ab. Conclusion: ID is associated with increased TG-Ab during the second trimester of pregnancy. Abbreviations: BMI = body mass index; CV = coefficient of variation; FT4 = free thyroxine; Hb = hemoglobin; ID = iron deficiency; IDA = iron deficiency anemia; SF = serum ferritin; T3 = triiodothyronine; T4 = thyroxine; TAI = thyroid autoimmunity; TG = thyroglobulin; TG-Ab = thyroglobulin antibody; TPO = thyroid peroxidase; TPO-Ab = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone.

A Case of Pituitary Insufficiency in a Patient Presenting with Hyponatremia: Might Be Slow-Progressing Lymphocytic Hypophysitis as a Possible Cause of Empty Sella?

Case: A 75-year-old female patient presented with complaints of nausea, weakness, fatigue and generalized pain all over her body. Her medical history included essential hypertension, type 2 Diabetes Mellitus, coronary artery disease and hypothyroidism. She was hospitalized due to detecting a serum sodium (Na) concentration of 123 mmol/L. Although her diuretic medications were discontinued and fluid replacement with parenteral hypertonic saline infusion was instituted for approximately 6 days, Na level did not return to normal. Secondary hypothyroidism was considered due to laboratory test results showing low fT4 level and markedly suppressed TSH value. Since further laboratory workup showed that TSH, ACTH, PRL, GH and gonadotropins were also low, the diagnosis was confirmed as “panhypopituitarism”. Her obstetric history was not suggestive of Sheehan’s Syndrome and she did not have a history of head injury or cerebrovascular disease. She was started on parenteral 100 mg hydrocortisone and hormonal replacement therapy with oral levothyroxine. The clinical picture of the patient improved dramatically with resolution of hyponatremia. Results and Discussion: Lymphocytic hypophysitis is an autoimmune disorder of the pituitary gland and it mostly affects middle-aged women. The fact that our patient was the age of 75 without having any clinical symptoms, since she had “panhypopituitarism” and a “partially empty sella” appearance in her pituitary MRI scans, “lymphocytic hypophysitis” was considered as the probably cause of pituitary insufficiency even if her age was older than the typical age of patients affected by the condition. Conclusion: It suggests that slow-progressing primary hypophysitis (probably lymphocytic hypophysitis) can lead to pituitary insufficiency at a later age.

Perioperative Low Tetraiodothyronine Levels and Adverse Outcomes After Heart Transplantation: A Retrospective, Observational Study

Thyroid dysfunction has been shown to be associated with increased all-cause mortality and severity of chronic heart failure in critical illness and severe cardiac diseases. The present study was conducted to ascertain the relationship between perioperative free triiodothyronine and free tetraiodothyronine (fT4) levels and postoperative adverse outcomes after heart transplantation (HTX). Retrospective, observational study. Single-center study in a quaternary care university clinical center. The study comprised adult patients who underwent HTX between 2015 and 2019 and had at least 1 perioperative thyroid hormone laboratory test on the day of surgery or in the 24 hours before/after the procedure (free triiodothyronine, fT4, and thyroid-stimulating hormone). No interventions were applied. The primary outcome was primary graft dysfunction (PGD), defined by the consensus conference of the International Society for Heart and Lung Transplantation. A total of 151 patients were included in the final analyses. Twenty-nine (19.2%) patients had PGD. Fourteen (9.3%) patients had low fT4 levels. An independent association was found between fT4 and PGD (odds ratio 6.49; 95% confidence interval 2.26-18.61; p = 0.001), with adjusted multivariate Cox regression models. The perioperative fT4 level could be a prognostic marker of adverse outcomes in HTX. The authors suggest appropriate perioperative monitoring of fT4 levels. Additional research is warranted to examine the optimal timing, dosage, and method of replacement.

Pure T3 thyrotoxicosis from a Struma Ovarii characterised by a paradoxical rise in thyroxine on treatment.

SummaryA 33-year-old female presented with a right 11.6 cm ovarian cyst. Routine pre-operative thyroid function tests showed thyroid stimulating hormone (TSH) of less than 0.02 mU/L (0.3–3.05) and a free thyroxine (FT4) of 5.5 pmol/L (10–28.2) suggesting either assay interference, triiodothyronine (T3) ingestion or hypopituitary hypothyroidism. A free triiodothyronine (FT3) level was requested which was high normal 6.9 pmol/L (3.1–8.1). Parallel assays on a different platform were similar but with a raised FT3 of 7.2 pmol/L (3.1–6.8). TSH receptor stimulating antibody (TSHAb) and thyroid peroxidase antibodies (TPO) were negative. Antithyroglobulin antibody (TgAb) was positive at 155.6 IU/mL (0–115). She was clinically euthyroid. Thyroid ultrasound showed a normal sized mildly heterogeneous gland with low blood flow and a solitary 1.5 cm U3 (BTA) nodule with higher blood flow. Thyroid Tc99m uptake was very low 0.2% (0.6–3.0) with no nodule uptake. These results demonstrated an extrathyroidal source of excessive autonomous T3 production resulting in the low thyroxine (T4). With carbimazole her TSH rose to 11.9 mU/L, FT4 rose to 7.7 pmol/L and FT3 reduced to 3.6 pmol/L. Histological diagnosis was Struma Ovarii. Her TSH, FT4 and FT3 remained normal thereafter. In conclusion, an extrathyroidal source of high T3 secretion was diagnosed using routine thyroid tests and scans. We believe this is the first description of a Struma Ovarii exclusively secreting T3 hormone characterised by the paradoxical rise of a low FT4 to normal with treatment. Two years later she developed non-secreting peritoneal deposits of highly differentiated follicular carcinoma.Learning points:Abnormally low TSH and FT4 levels suggestive of possible T3 ingestion, or less likely, hypopituitary hypothyroidism should always be followed by an assay of FT3.The diagnosis of an extrathyroidal source of T3 can be made using conventional thyroid tests, thyroid ultrasound scanning and technetium thyroid uptake and scan imaging. In a pre-menopausal patient this avoids a radiation dose to the pelvis.Pelvic radioisotope scanning of a suspected Struma Ovarii causing thyrotoxicosis can be reserved for patients whose thyroid function remains abnormal after initial surgery.Carbimazole is effective in the treatment of extrathyroidal autonomous T3 hormone production from a Struma Ovarii.The pathological appearance of a Struma Ovarii is not a guide to its malignancy. Even with a benign appearance they can disseminate to peritoneum, as highly differentiated follicular carcinoma (previously known as peritoneal strumosis).Hyperthyroid secretion by a Struma Ovarii may not be replicated in the metastatic follicular carcinoma in the peritoneum.

Effect of Donepezil and Vitamin B12 Supplement on Serum Thyroid Profile in Alzheimer’s Disease

Aims: The aim of this study was to investigate thyroid status in Alzheimer’s Disease (AD) patients and its response to donepezil and vitamin B12 supplement therapy for 6 months.&#x0D; Design: Case-Control Observational study.&#x0D; Place and Duration: Department of Biochemistry, GGMC &amp; Sir J. J. Group of Hospitals, Mumbai, India between March 2017 and July 2019.&#x0D; Methodology: Case-Control study comprised of 71 AD patients and 70 healthy controls above 60 years of age. Blood serum samples were analyzed for thyroid hormones levels by the chemiluminescence method. AD patients were treated with donepezil (5 mg/day) and vitamin B12 supplement (1.5 mg/day) and thyroid profile was observed at intervals of 3 and 6 months. Statistical evaluation was done by using IMB SPSS statistics version 25.&#x0D; Results: Serum levels of thyroid hormones were low in euthyroid AD patients when compared with controls at the baseline level [T3 (120.64 ± 20.64 vs 127.8 ± 17.29), T4 (7.71 ± 2.34 vs 7.54 ± 1.85), FT3 (1.2 ± 0.13 vs 2.26 ± 0.63) and FT4 (0.79 ± 0.08 vs 1.29 ± 0.27)] except TSH which was increased in AD [TSH (2.71 ± 1.19 vs 2.34 ± 0.65)]. During follow-ups at 3 and 6 months, there was a slight decrease in TSH levels in response to the therapy.&#x0D; Conclusion: The AD patients were euthyroid with low T3, FT3 and FT4 serum levels and high TSH serum levels. Thyroid hormones might play a role as markers for disease progression. Donepezil and vitamin B12 therapy could not benefit restore the normal thyroid functioning in a period of 6 months. Further longitudinal research with larger cohort might help in elucidating thyroid dysfunction in AD and develop novel therapeutic strategies.

Thyroid hormones profile among obese pregnant Sudanese women

Previous studies evaluating thyroid function among obese pregnant women failed to demonstrate a consistent pattern of thyroid hormones profile, probably due to the variations in biological/environmental determinants of thyroid function in different countries. The aim of the study was to evaluate thyroid hormones profile in Sudanese pregnant women with varying degrees of obesity. Obstetric/sociodemographic characteristics were gathered from 178 singleton pregnant Sudanese women using questionnaires. Weight and height were measured; body mass index (BMI) was calculated and categorized into four groups: Underweight (BMI <18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2). Free triiodothyronine (FT3), free thyroxin (FT4), and thyroid-stimulating hormone (TSH) were measured. Of the 178 enrolled women, 9 (5.1%), 52 (29.2%), 73 (41.0%), and 44 (24.7%) were underweight, normal BMI, overweight, and obese, respectively. FT3 level was significantly higher in obese women compared with normal BMI (P=0.004) as well as overweight women (P=0.015). Higher FT3 levels were significantly associated with obesity (odds ratio [OR]=9.5, 95% confidence interval [CI] =3.1-29.0, P<0.001). Lower levels of FT4 were significantly associated with overweight (OR=0.06, 95% CI=0.007-0.58, P=0.015) and obesity (OR=0.048, 95% CI=0.004-0.5, P=0.018). Based on linear regression analysis, BMI was positively associated with FT3 (4.7 pmol/l, P<0.001) and negatively associated with FT4 (-8.26 pmol/l, P=0.001). BMI correlates with FT3 differently compared to FT4. Pregnant women with higher BMI are likely to have higher levels of FT3, but lower FT4. In contrast, TSH levels were comparable in different BMI groups. Increased iodothyronine 5´deiodinase (5´D) activity associated with obesity may give an explanation for thyroid profile in those with higher BMI. High 5´ activity increases FT3 at the expense of FT4. Alternatively, high FT3 and low FT4 are expected to feedback differently on TSH, which explains the loss of positive correlation between BMI and TSH.

Nocturnal haemodialysis is associated with a reduced occurrence of low triiodothyronine serum levels in haemodialysed patients.

BackgroundEnd-stage renal disease (ESRD) is associated with a broad spectrum of morphological and functional thyroid disorders. Recent studies have shown that low free triiodothyronine (fT3) levels are related to inflammatory status and endothelial activation in ESRD patients on haemodialysis (HD). Limited data exist about a possible relationship between dialysis regimen, namely long nocturnal haemodialysis (LNHD), and thyroid function parameters. The aim of this study was to evaluate the relationship between dialysis regimen and thyroid function, and consequently with the main patient outcomes.MethodsTo this purpose, we performed a retrospective, single-centre cohort study including 220 incident chronic HD patients treated during an 8-year period (from January 2010 to December 2017). The main clinical and haematochemical parameters, including thyroid function, were evaluated and related to the main patient outcomes.ResultsPatients with low fT3 levels (<3.05 ng/mL) showed significantly lower survival rates than patients with normal fT3 levels (>3.05 ng/mL) (P < 0.001), although there were no substantial differences in the demographic and clinical characteristics between the two groups. After propensity score 1:3 matching of 25 patients treated with nocturnal HD to 75 patients treated with diurnal HD, LNHD patients showed significantly higher survival rates (88.0% versus 61.3%, P = 0.001) and lower incidence of cardiovascular events than patients on diurnal dialysis (8.0% versus 40.0%, P = 0.001). Moreover, an 8-year time-dependent analysis showed that at any time, except for baseline, the rate of patients with fT3 levels >3.05 ng/mL was significantly higher in LNHD patients than in patients treated with diurnal dialysis.ConclusionsOur data suggest that the application of alternative dialysis regimens, also reducing the frequency of low T3, could ameliorate outcomes and therefore reduce the incidence of cardiovascular events in HD patients.