Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis and apathy especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down’s Syndrome

IntroductionThyroid dysfunctions are one of the most common abnormalities coexisting in children with Down’s syndrome (DS) and have been reported in up to 54% of cases.Aim of the StudyThe purposes of this retrospective study were to investigate the course of subclinical hypothyroidism in children with DS, to evaluate the thyroid function of these subjects in relation to the risk of developing overt thyroid disease and autoimmunity, and to identify clinical and biochemical characteristics of patients prescribed L-T4 therapy in children and adolescents with DS and SH.Material and MethodsThe records of DS patients referred to the Endocrinology Outpatient Clinic between 2010 and 2015 for screening of thyroid function were observed till the end of 2019 June and analyzed retrospectively. The children diagnosed with congenital hypothyroidism, acute lymphoblastic leukemia, and seizures and treated with drugs that may have interfered with thyroid function like lithium, antiepileptic, or iodinated drugs and glucocorticoids were excluded from the study.ResultsThe data of 77 DS patients were collected, evaluated, and analyzed. The study group consisted of 73 patients (32 girls and 41 boys with the mean age at baseline of 3.0 ± 4.5 years). A total of 63/73 (87%) children were diagnosed with SH. The 16/63 (25.4%) patients were followed-up without the treatment (group SH-T0), and therapy with levothyroxine (L-T4) was introduced in 47/63 (74.6%) SH children with a mean dosage of 1.8 ± 1.0 μg/kg/day (group SH-T1). Thyroxine supplementation did not improve growth expressed as ΔhSDS (0.1 ± 1.3, ranged −2.1 to 3.8 in SH-T0 vs. 0.0 ± 0.7, ranged −1.7 to 1.4 in SH-T1, p = 0.96) and ΔBMI Z-score (0.3 ± 0.9, ranged −0.9 to 2.6 in SH-T0 vs. 0.3 ± 1.1, ranged −2.1 to 2.9 in SH-T1, p = 0.65). Positive anti-TPO and anti-TG antibodies were detected in 7/63 (11.1%) DS cases.ConclusionsSH is the most frequent presentation of thyroid gland dysfunction in DS children. A small percentage of patients develop an overt hypothyroidism, particularly in females with mostly positive titer of antithyroid autoantibodies.

Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study

Purpose: The association between subclinical hypothyroidism (SCH) and cardiovascular risk, particularly with a TSH <10 µIU/ml, remains controversial. The objective of our study was to assess the association between SCH and cardiovascular risk through carotid intima-media thickness, and alternatively, to evaluate its change after treatment with levothyroxine. Methods: A total of 54 individuals were included in the study: 18 with SCH; 18 with overt hypothyroidism (OH); and 18 healthy controls (HC). The carotid intima-media thickness was measured in each group. In SCH, follow-up was performed at three and six months after the start of levothyroxine treatment. Results: The mean age of the total population at baseline was 35.8 years. The median TSH in SCH was 6.15 µIU/ml. The carotid intima-media thickness (mean and standard deviation) was greater in SCH in comparison to the HC group: right common carotid artery (RCCA), 0.486 ± 0.106 mm and 0.413 ± 0.075 mm in SCH and HC, respectively, p=0.01 and left common carotid artery (LCCA), 0.511 ± 0.144 mm and 0.427 mm ± 0.090 in SCH and HC, respectively, p=0.03). In patients with SCH, there was a decrease in the carotid intima-media thickness after treatment with levothyroxine (RCCA and LCCA, p <0.05 at three and six months). Conclusions: There was an association between increased carotid intima-media thickness in patients with SCH in comparison with HC, even with a TSH <10 µIU/ml. The increase was reversed with levothyroxine therapy. The association of this increased thickness with important cardiovascular outcomes remains uncertain and should be evaluated in future studies.

Autoimmune thyroid disease in diabetic children and adolescents: a single center study from south Punjab

Objective: To evaluate the prevalence of autoimmune thyroid disease (AITD) in diabetic children in south Punjab. Methods: This was an observational cross sectional study from Jan 2019 to Dec 2019 in the outpatient diabetic clinic of the department of pediatric endocrinology at Children Hospital and The Institute of Child Health Multan. A total of 161 consecutive patients of both genders with TIDM were enrolled in this study after taking informed consent. Blood samples for Thyroid functions testes including thyroid stimulating hormone (TSH), free thyroxin (fT4), Thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TG-Ab) and glycosylated hemoglobin (HbA1C) level were sent. Results: Among diabetic children males were 83 (51.6%). Age range was 2-15 years. Mean age and standard deviation was 9.7± 4.3. TPO-Ab was positive in 34 patients (21.1%) and TG-Ab in 27 patients (16.7%), whereas both antibodies were positive in 17 patients (10.5%). Six patients (3.7%) had evidence of subclinical hypothyroidism, 8 patients (4.9%) had overt hypothyroidism and 1 patient (0.62%) had hyperthyroidism Conclusion: The prevalence of AITD among children and adolescents with type 1 diabetes mellitus was 21.1% in our study. Hypothyroidism was more prevalent in these children compared to hyperthyroidism. All diabetic children should be screened for AITD. Thyroid functions should be checked where TPO antibody is positive. Keywords: Autoimmune thyroid disease, anti thyroid peroxidase antibody, anti thyroglobulin Continuous...

Postpartum Thyroid Dysfunction in Women With Known and Newly Diagnosed Hypothyroidism in Early Pregnancy

BackgroundHypothyroidism in the first trimester of pregnancy (T1) has great adverse effects on mothers and foetuses. However, few studies have investigated the influence on postpartum thyroid dysfunction. This study aimed to evaluate their long-term effect on postpartum thyroid function within one year after delivery.MethodsIn total, 151 women were recruited from 1496 participants and were classified as newly diagnosed subclinical hypothyroidism (SCH) in T1 (ND-SCH, n=50), previously known SCH before pregnancy (PK-SCH, n=51) and previously known overt hypothyroidism (PK-OH, n=50). Their thyroid functions were dynamically monitored from pre-conception to one-year postpartum.ResultsDuring pregnancy, the first thyroid functions’ test time in T1 were 5-8 gestational weeks. After delivery, the prevalence of postpartum thyroiditis (PPT) was comparable in women with previously known and newly diagnosed hypothyroidism [ND-SCH 62.0% vs PK-SCH 64.7% vs PK-OH 64.0%, P=0.96]. For the ND-SCH group, PPT was significantly related with thyroid-stimulating hormone (TSH) &gt;4.0 mU/L occurring at &lt;8 gestational weeks [OR=8.06, 95% CI, 2.08-31.29] and TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.73, 95% CI, 1.04-13.41]. For patients with known hypothyroidism before pregnancy (PK-SCH and PK-OH), TSH&gt;2.5 mU/L in T1 [OR=3.55, 95% CI, 1.43-8.81] and TPOAb≥300 μIU/mL [OR=6.58, 95% CI, 2.05-21.12] were associated with PPT. Regardless of whether SCH was diagnosed before pregnancy or in T1, the levothyroxine (LT4) treatment was discontinued at delivery. More than 50% of the patients had to face the hypothyroidism phase of postpartum and restarted LT4 treatment in the first-year follow-up. The logistic regression analysis revealed that TSH elevation occurring at &lt;8 gestational weeks [OR=2.48, 95% CI, 1.09-5.6], TSH levels outside 1.0-2.5 mU/L near childbirth [OR=3.42, 95% CI, 1.45-8.05], and TPOAb≥300 μIU/mL [OR=6.59, 95% CI, 1.79-24.30] were the risk factors.ConclusionTSH elevation at &lt;8 gestational weeks was associated with PPT after delivery in women with known and newly diagnosed hypothyroidism. Especially for SCH patients who stopped LT4 treatment at delivery, unsatisfactory TSH level at &lt;8 gestational weeks and near childbirth, TPOAb≥300 μIU/mL were the risk factors for LT4 retreatment in one-year postpartum.

A STUDY TO EVALUATE THE THYROID FUNCTION IN SERO POSITIVE RHEUMATOID ARTHRITIS

Background: The thyroid dysfunction in rheumatoid arthritis is well-known but unfortunately there are only few studies available in our country to assess the thyroid function in RA patients. Methods: It was a Hospital based observational, descriptive study . Upgraded department of General Medicine, SMS Medical College and AttachedHospitals, (Jaipur). Results: Maximum patients 208(80.00%) are euthyroid followed by 28(10.77%) are overt - hypothyroidism, 22(8.46%) subclinical hypothyroidism and 2 patients (0.77%) are subclinical hyperthyroidism patients Conclusion: Prevalence of thyroid dysfunctions in rheumatoid arthritis is high and associated with thyroid autoimmunity and suggested that allrheumatoid arthritis patients should go for thyroid functions. Hence, it is advisable to screen the patients of rheumatoid arthritis for thyroid dysfunction so that early identification and treatment can provide a healthier life ahead. Keywords: NAFLD, TSH, T3, T4.

Association between thyroid hormones and insulin resistance indices based on the Korean National Health and Nutrition Examination Survey

Thyroid dysfunction has been implicated as a potential pathophysiological factor in glucose homeostasis and insulin resistance (IR). This study aimed to identify the correlation between thyroid dysfunction and IR. We used data from the sixth Korean National Health and Nutrition Examination Survey to evaluate a total of 5727 participants. The triglyceride glucose (TyG) index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated to represent IR. Correlation analysis was performed between thyroid dysfunction and IR. The log-transformed TSH (LnTSH) and free T4 were significantly correlated with the TyG index (TSH, beta coefficient 0.025, 95% confidence interval [CI] 0.014–0.036, p < 0.001; free T4, − 0.110 (− 0.166 to − 0.054), p < 0.001) but not HOMA-IR. Overt hypothyroidism is correlated with increased TyG index in pre-menopausal females (0.215 (0.122–0.309) p < 0.001). On the other hand, overt hyperthyroidism is correlated with increased HOMA-IR in males (0.304 (0.193–0.416), p < 0.001) and post-menopausal females (1.812 (1.717–1.907), p < 0.001). In euthyroid subjects, LnTSH and TyG index were significantly correlated in females. In conclusion, both hyperthyroidism and hypothyroidism might be associated with IR but by different mechanisms. It might be helpful to assess IR with appropriate indexes in patients with thyroid dysfunction.

Angiopoietin-like protein 3, 4 and 8 are linked to cardiovascular function in naïve sub-clinical and overt hypothyroid patients receiving levothyroxine therapy

Objective: Angiopoietin-like protein (ANGPTL) 3,4,8 are upcoming cardiovascular biomarkers. Experimental studies showed thyroid hormones altered their levels. We assessed: ANGPTL3,4,8 as predictor of cardiovascular functions among naïve-subclinical and naïve-overt hypothyroidism [SCH and OH]; and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function. Design and Methods: Prospective follow-up study assessed ANGPTL3,4,8 levels, vascular status (flow mediated dilation% of brachial artery (FMD%), carotid intima media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), LV mass), well-known cardiovascular risk factors and HOMA-IR, at two time points: among naïve -SCH, naïve-OH and healthy subjects groups; and at six months after achieved euthyroid state with LT4 with calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4- hypothyroid groups. Results: Significantly elevated ANGPTL3,4 and 8 among hypothyroid groups than healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL levels: ANGPTL3,4 for impaired FMD% and ANGPTL8 for LVmass among naïve-SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve-OH; ∆↓ ANGPTL3 for ∆↓ ASI meanwhile ∆↑ freeT4 for ∆↓ ANGPTL3, ∆↓ fasting glucose, ∆↓ triglyceride and ∆↓ thyroid peroxidase antibody for ∆↓ ANGPTL4 among LT4-SCH. ∆↓ ANGPTL4 for ∆↓ MPI and ∆↓ LVmass meanwhile ∆↓ TSH and ∆↓ triglyceride for ∆↓ ntributors for ANGPTL level: ANGPTL3,4 for impaired FMD% and ANGPTL8 for LVmass among naïve-SCH; ANGPTL3 for EF% and g LT4-OH. Conclusion: Elevated ANGPTL3,4,8 levels are differentially independent predictors of endothelial and cardiac function and reduced with LT4 in SCH and OH.

Isfahan Thyroid Cohort Study (ITCS)

Background: The Isfahan Thyroid Cohort Study (ITCS) is one of the few population-based epidemiological studies in Iran that investigates the prevalence and incidence of thyroid disorders including hypothyroidism, hyperthyroidism, goiter, nodule, and iodine status. Methods: This cohort is located in Isfahan, Iran. The first phase was initiated in 2006 with 2523 participants (1275 males, 1248 females). The participants were selected using multi-stage cluster sampling from the general residents of Isfahan, Iran. The study had two phases (2006 and 2011) and its third stage is planned for 2020–2021. Results: The prevalence of thyroid function states was euthyroid (89.3%, 95% CI: 88%–90%), overt hypothyroidism (2.8%, 95% CI: 2%‒3%), subclinical hypothyroidism (5.8%, 95% CI: 4%–6%), overt hyperthyroidism (0.8%, 95% CI: 0.4%‒1%), and subclinical hyperthyroidism (0.99%, 95% CI: 0.6%–1%). Hypothyroidism and hyperthyroidism were significantly associated with goiter. The incidence of thyroid dysfunction was reported as follows: overt hypothyroidism (2.7, 95% CI: 1.6–3.7), subclinical hypothyroidism (20.6, 95% CI: 18–23), overt hyperthyroidism (1.9, 95% CI: 1–2.7) and subclinical hyperthyroidism (2.7, 95% CI: 1.6–3.7) per 1000 (person-year). Conclusion: We assessed the prevalence and incidence of thyroid disorders in Isfahan in the first and second phase, respectively. We are conducting the third phase of the ITCS in order to study the associations between thyroid peroxidase antibody (TPOAb) level and environmental factors such as infection.

Prevalence of cardiometabolic risk factors in patients with hypertension and subclinical hypothyroidism

It is known that the presence of overt hypothyroidism carries additional risks of developing cardiovascular diseases due to impaired lipid and carbohydrate metabolism. But whether subclinical hypothyroidism (SH) has the same negative impact is still controversial. The assessment of its role is especially important in patients with existing arterial hypertension (AH) in the early stages of the disease in order to prevent future complications. The aim of this work is to identify and assess the prevalence of early cardiometabolic risk factors in patients with AH combined with SH. Materials and methods. 66 patients (55.4 % women) aged from 25 to 59 years with a median age of 51.1 years were included in the study during 2019–2020 years. All the patients were divided into 3 groups, randomized by age and sex: group 1 (n = 21) – vo­lunteers without AH and SH; group 2 (n = 25) – euthyroid patients with stage 1–2 grade 1–2 AH and low-to-moderate cardiovascular risk (CVR); group 3 (n = 20) – patients with stage 1–2 grade 1–2 AH and low-to-moderate CVR in combination with SH. Blood pressure was measured, anthropometric data were assessed, glucose levels and lipid profile indicators were determined in all patients. Results. Comparative characteristics of the groups showed a rise in the frequency of detecting increased waist circumference and the waist-to-hip ratio, obesity, metabolic syndrome, its individual components and lipid profile disorders, especially the levels of total cholesterol and high-density lipoprotein cholesterol in patients with SH even in the early stages of AH and CVR of low gradations. However, dyslipidemias in general and hypertriglyceridemia in particular were more common in euthyroid hypertensive patients compared to patients with AH and concomitant SH. There was also a tendency towards an increase in gynoid obesity and a worsening of the lipid and carbohydrate profile disorders in SH patients in comparison to euthyroid patients with AH, although the differences were not statistically significant. Conclusions. Evaluation of cardiometabolic risk factors revealed the increase in severity of female obesity and worsening of abnormalities in lipid and carbohydrate profiles with the SH development in patients even in the early stages of AH and low-CVR, that additionally increases the risk of cardiovascular complications.