The relationship between mental fatigue, depression, and cognition in Graves' disease.

Objective: Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism. Methods: A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment. Results: During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies. Conclusion: Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.

Thyroid Disorders and Development of Cognitive Impairment: A Review Study.

Dementia is a neurological disorder that is spreading with increasing human lifespan. In this neurological disorder, memory and cognition are declined and eventually impaired. Various factors can be considered as the background of this disorder, one of which is endocrine disorders. Thyroid hormones are involved in various physiological processes in the body; one of the most important of them is neuromodulation. Thyroid disorders, including hyperthyroidism or hypothyroidism, can affect the nervous system and play a role in the development of dementia. Despite decades of investigation, the nature of the association between thyroid disorders and cognition remains a mystery. Given the enhancing global burden of dementia, the principal purpose of this study was to elucidate the association between thyroid disturbances as a potentially modifiable risk factor of cognitive dysfunction. In this review study, we have tried to collect almost all of the reported mechanisms demonstrating the role of hypothyroidism and hyperthyroidism in the pathogenesis of dementia.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Effects of Chronic Suppression or Oversuppression of Thyroid-Stimulating Hormone on Psychological Symptoms and Sleep Quality in Patients with Differentiated Thyroid Cancer.

In differentiated thyroid cancer (DTC), the standard treatment includes total thyroidectomy and lifetime levothyroxine (LT4) replacement. However, long-term exogenous LT4 has become controversial due to the adverse effects of oversuppression. The study included 191 patients (aged 18-76 years) with a prospective diagnosis of non-metastatic DTC and 79 healthy individuals. The patients with DTC were stratified into three groups according to their TSH levels: suppressed thyrotropin if TSH was below 0.1 µIU/ml, mildly suppressed thyrotropin if TSH was between 0.11 and 0.49 µIU/ml, and low-normal thyrotropin if THS was between 0.5 and 2 µIU/ml. The Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Anxiety Sensitivity Index (ASI), Short Symptom Inventory (SSI), and Pittsburgh Sleep Quality Index (PSQI) were administered to all participants. It was found that the BDI, BAI, SSI and PSQI scores were worse in patients with DTC (p=0.024, p=0.014, p=0.012, and p=0.001, respectively). According to theTSH levels, the mean ASI was found to be higher in the suppressed and mildly suppressed thyrotropin groups (19±14.4 vs. 10.6±11.1; 16.4±14.9 vs. 10.6±11.1, p=0.024, respectively), the mean SSI was found higher in the suppressed group (61.0±55.5 vs. 35.1±37.0, p=0.046), and the mean PSQI was higher in all three groups (7.94±3.97 vs. 5.35±4.13; 7.21±4.59 vs. 5.35±4.13; 7.13±4.62 vs. 5.35±4.13, p=0.006) when compared with the controls. No significant difference was found between the groups. A positive correlation was detected in the duration of LT4 use and BDI and SSI, and a weak, negative correlation was detected between TSH levels and ASI and PSQI. Based on our study, it was found that depression, anxiety disorders, and sleep problems were more prevalent in patients with DTC, being more prominent in the suppressed TSH group. These results were inversely correlated with TSH values and positively correlated with the duration of LT4 use. Unnecessary LT4 oversuppression should be avoided in patients with DTC.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.

The role of coping strategies, depression and anxiety in thyroid disease / A megküzdési stratégiák, a depresszió és a szorongás szerepe a pajzsmirigybetegségekben.

Összefoglaló. Bevezetés: A tudományos szakirodalomban számos kérdés fogalmazódik meg a pajzsmirigybetegségeket befolyásoló pszichológiai tényezokrol. Kevés tanulmány készült a pajzsmirigybetegségek és a megküzdési stratégiák kapcsolatáról. Célkituzés: Jelen tanulmányunk célja felmérni a megküzdési stratégiák, a depresszió és a szorongás szintjének változásait a pajzsmirigybetegek (hyperthyreosis és hypothyreosis) esetében a gyógyszeres kezelés (Thyrozol és Euthyrox) hatására. Módszer: A betegeket a szakorvos diagnózisa, illetve a TSH- és fT4-szint alapján hyperthyreosis- (n = 10) és hypothyreosis- (n = 21) csoportba soroltuk. Mindkét csoport tagjait az endokrinológiai kezelés elott és után pszichológiai felmérésnek vetettük alá. A felmérés során a megküzdési stratégiák felméréséhez a következo skálákat alkalmaztuk: Kognitív Érzelem Szabályozás Kérdoív (Cognitive Emotion Regulation Questionnaire - CERQ), Hobfoll-féle Megküzdési Stratégia Kérdoív (Strategic Approach to Coping Scale - SACS). A Beck Depresszió Kérdoívet (Beck Depression Inventory - BDI-II) alkalmaztuk a depresszió felmérésére, az Állapot- és Vonásszorongás Kérdoívet (State-Trait Anxiety Inventory, Form Y - STAI-Y) a szorongás szintjének felmérésére. Eredmények: A két csoport pszichológiai és laboreredményeit összehasonlítottuk a gyógyszeres kezelés elott és után. Mind a hyperthyreosisban, mind a hypothyreosisban szenvedo betegeknél magas volt a depresszió és a szorongás szintje. A hyperthyreosisban szenvedo betegeknél a depresszió magasabb. A gyógyszeres kezelés után a depresszió és a szorongás szintje csökkent mindkét csoportban, a megküzdési stratégiák többnyire változatlanok maradtak. Következtetések: Pajzsmirigybetegeknél a kognitív viselkedésbeli pszichoterápiás beavatkozás a gyógyszeres kezelés kiegészíto alternatívája lehet a szorongás és a depresszió szintjének csökkentése és a diszfunkcionális megküzdési stratégiák módosítása szempontjából. Orv Hetil. 2021; 162(7): 262-268. INTRODUCTION: There is a high interest in the scientific literature in psychological factors that influence the course of thyroid disease. There are a few studies on the link between thyroid disease and coping strategies. OBJECTIVE: In the present study, we aimed to evaluate the manifestation of depression, anxiety and coping strategies in people with thyroid disease and the impact of endocrinological medication on these psychologic items. METHOD: The patients were grouped into two groups, hyperthyroid (n = 10) and hypothyroid (n = 21), according to the diagnosis established by the attending physician, TSH and fT4 level. Patients with hyperthyroidism and hypothyroidism were evaluated before and after endocrinological treatment with the Cognitive Emotion Regulation Questionnaire (CERQ), Strategic Approach to Coping Scale (SACS) for the evaluation of coping strategies, Beck Depression Inventory (BDI-II) for assessing the level of depression, State-Trait Anxiety Inventory, Form Y (STAI-Y) for assessing anxiety. These two groups have been compared. RESULTS: The psychological and laboratory results of the two groups were compared before and after drug treatment. Both patients with hyperthyroidism and with hypothyroidism had high levels of depression and anxiety. In hyperthyroidism, depression is more severe. Following treatment with Thyrozol and Euthyrox, the level of depression and anxiety decreases in patients with hyper- and hypothyroidism; the coping strategies remained almost unchanged. CONCLUSION: Cognitive-behavioral psychotherapeutic intervention could be supplementary to drug treatment in terms of reducing anxiety, depression, and modifying dysfunctional coping strategies for patients with thyroid diseases. Orv Hetil. 2021; 162(7): 262-268.

Outcomes of Thyroid Dysfunction in People Aged Eighty Years and Older: An Individual Patient Data Meta-Analysis of Four Prospective Studies (Towards Understanding Longitudinal International Older People Studies Consortium).

Background: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older. Methods: Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality. Results: Of the total 2116 participants at baseline (mean age 87 years, range 80-109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6-1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7-1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8-1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4-5.9]). Results did not differ after excluding participants using thyroid-influencing medication. Conclusions: In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance.

Altered attention networks in patients with thyroid dysfunction: A neuropsychological study.

Patients with thyroid dysfunction (31 hypothyroid, 32 subclinical hypothyroidism, 34 hyperthyroid, and 30 subclinical hyperthyroidism) and 37 euthyroid control subjects were recruited and performed the attention network test (ANT), which can simultaneously examine the alertness, orientation and execution control of the participants. Patients with hypothyroidism had abnormalities in the alerting network, and those with hyperthyroidism had impairments of the alerting and executive control networks. No attention networks deficit existed in patients with subclinical hyperthyroidism and subclinical hypothyroidism. The anxiety and depression scores of patients with thyroid dysfunction were significantly higher than those of the healthy control group. Covariance analysis demonstrated that interactions between group and Hamilton Anxiety Scale scores, group and HAMD score were not significant, but there was a significant main effect for group when analyzing the difference in values of the alerting network between groups. Further, the efficiency of the executive control network was negatively correlated with the T4 level in the hypothyroidism group, and positively correlated with the T4 level in the hyperthyroidism group. T4 or T3 level and efficiencies of the executive control network had a significant quadratic U-shaped relationship in all participants. In summary, the patients with four kinds of thyroid dysfunction exhibited different characteristics of ANT performance. Patients with thyroid dysfunction had various degrees of anxiety and depression disorders, but anxiety and depression disorders had no effect on the differences in the executive control network between the groups.

Mental Health Conditions and Hyperthyroidism.

OBJECTIVES: To evaluate the proportion of pediatric patients with concurrent diagnoses of hyperthyroidism and mental health conditions (MHCs) by using the Military Health System database. We hypothesized that the prevalence of mental health disorders would be higher in patients with hyperthyroidism compared with in the nonhyperthyroid population. METHODS: The prevalence of hyperthyroidism and MHCs was calculated by using data extracted from the Military Health System Data Repository on military beneficiaries between 10 and 18 years old who were eligible to receive care for at least 1 month during fiscal years 2008 through 2016. Prevalence ratios were used to compare MHC diagnoses in those with versus without a diagnosis of hyperthyroidism. RESULTS: There were 1894 female patients and 585 male patients diagnosed with hyperthyroidism during the study period. Prevalence ratios for MHCs in those with versus without hyperthyroidism ranged from 1.7 (attention-deficit/hyperactivity disorder [ADHD]) to 4.9 (bipolar disorder). Strikingly, suicidality was nearly 5 times more likely in patients diagnosed with hyperthyroidism than in patients who were never diagnosed with hyperthyroidism. For each of the MHCs examined, with the exception of suicidality, the MHC diagnosis was more commonly made before the diagnosis of hyperthyroidism, with the highest proportion of patients being diagnosed with ADHD before receiving a diagnosis of hyperthyroidism (68.3%). CONCLUSIONS: There is a clear association between hyperthyroidism and each of the following MHCs: ADHD, adjustment disorder, anxiety, bipolar disorder, depression, and suicidality. This study highlights the need to consider this association when evaluating patients with overlapping symptoms and for effective mental health screening tools and resources for clinicians.

Age effect on thyroid hormone brain response in male mice.

PURPOSE: Thyroid hormones (TH) are important for brain development and central nervous system (CNS) function. Disturbances of thyroid function occur with higher prevalence in the ageing population and may negatively impact brain function. METHODS: We investigated the age impact on behavior in young adult and old male mice (5 vs. 20 months) with chronic hypo- or hyper-thyroidism as well as in sham-treated controls. Expression of TH transporters and TH responsive genes was studied in CNS and pituitary by in situ hybridization and qRT-PCR, whereas TH serum concentrations were determined by immunoassay. RESULTS: Serum TH levels were lower in old compared with young hyperthyroid mice, suggesting a milder hyperthyroid phenotype in the aged group. Likewise, elevated plus maze activity was reduced in old hyperthyroid animals. Under hypothyroid conditions, thyroxine serum concentrations did not differ in young and old mice. Both groups showed a comparable decline in activity and elevated anxiety levels. However, an attenuated increase in hypothalamic thyrotropin releasing hormone and pituitary thyroid stimulating hormone transcript expression was found in old hypothyroid mice. Brain expression of monocarboxylate transporter 8 and organic anion transporting polypeptide 1c1 was not affected by age or TH status. CONCLUSIONS: In summary, ageing attenuates neurological phenotypes in hyperthyroid but not hypothyroid mice, which fits with age effects on TH serum levels in the animals. In contrast no changes in TH transporter expression were found in aged mouse brains with hyper- or hypo-thyroid state.

Changes in thyroid hormone activity disrupt photomotor behavior of larval zebrafish.

High throughput in vitro, in silico, and computational approaches have identified numerous environmental chemicals that interfere with thyroid hormone (TH) activity, and it is posited that human exposures to such chemicals are a contributing factor to neurodevelopmental disorders. However, whether hits in screens of TH activity are predictive of developmental neurotoxicity (DNT) has yet to be systematically addressed. The zebrafish has been proposed as a second tier model for assessing the in vivo DNT potential of TH active chemicals. As an initial evaluation of the feasibility of this proposal, we determined whether an endpoint often used to assess DNT in larval zebrafish, specifically photomotor behavior, is altered by experimentally induced hyper- and hypothyroidism. Developmental hyperthyroidism was simulated by static waterborne exposure of zebrafish to varying concentrations (3-300 nM) of thyroxine (T4) or triiodothyronine (T3) beginning at 6 h post-fertilization (hpf) and continuing through 5 days post-fertilization (dpf). Teratogenic effects and lethality were observed at 4 and 5 dpf in fish exposed to T4 or T3 at concentrations >30 nM. However, as early as 3 dpf, T4 (> 3 nM) and T3 (> 10 nM) significantly increased swimming activity triggered by sudden changes from light to dark, particularly during the second dark period (Dark 2). Conversely, developmental hypothyroidism, which was induced by treatment with 6-propyl-2-thiouracil (PTU), morpholino knockdown of the TH transporter mct8, or ablation of thyroid follicles in adult females prior to spawning, generally decreased swimming activity during dark periods, although effects did vary across test days. All effects of developmental hypothyroidism on photomotor behavior occurred independent of teratogenic effects and were most robust during Dark 2. Treatment with the T4 analog, Tetrac, restored photomotor response in mct8 morphants to control levels. Collectively, these findings suggest that while the sensitivity of photomotor behavior in larval zebrafish to detect TH disruption is influenced by test parameters, this test can distinguish between TH promoting and TH blocking activity and may be useful for assessing the DNT potential of TH-active chemicals.

Prenatal thyroxine treatment promotes anxiolysis in male Swiss mice offspring.

The proper functioning of the maternal thyroid plays a crucial role in fetal development. Thus, the aim of our study was to verify how maternal hyperthyroidism is able to change behavioral parameters in mice offspring during adulthood. For this purpose, pregnant Swiss mice (n = 24 and ~35 g) were randomly assigned into two groups: a control and a thyroxine (T4)-treatment group. The control was treated with 0.9% saline, while the treatment group received T4 (200 µg/kg, s.c.) once daily during the entire pregnancy period. After completing 70 days of life, a part of male offspring underwent a battery of tests, including open field, dark-light box, elevated plus maze, marble burying, rotarod and tail suspension tests. The other male pups were euthanized, being hippocampus and serum collected for RNA analysis and hormones measurement, respectively. Statistical analysis was performed using Student's t-test, and the means were considered significantly different when p < 0.05. In adult offspring, a significant decrease was observed for serum T3 in treated group. It was demonstrated that the T4 group had an increase in total distance traveled in an open field test. In the elevated plus maze test, we observed a higher time in opened arms as well as an increased in percentage of entries in these arms. In the hippocampus, T4 offspring had a higher expression of tryptophan hydroxylase 2 (TPH2), serotonin transporter (SERT) and glutamate decarboxylase 67 (GAD 67) in comparison to controls. These findings suggest that prenatal T4 treatment alters hippocampal serotonergic and GABAergic systems, promoting anxiolysis in male adult offspring.

The relationship between quality of life, cognition, and thyroid status in Graves' disease.

PURPOSE: To assess quality of life (QoL) and cognitive function among Graves' disease (GD) patients with different thyroid status, with and without ophthalmopathy. METHODS: This is a cross-sectional clinic-based study involving 154 patients with GD (81.27% were female, mean age 45.6 ± SD 11.2 years) and 54 (35.06%) had ophthalmopathy. Data were collected after an informed consent from all patients was obtained. All patients completed the 36-Item Short Form Health Survey and Mini-Mental State Examination. Patients with ophthalmopathy also completed the Graves' Orbitopathy Quality of Life Questionnaire. RESULTS: Patients with hyperthyroidism presented a greater impairment in QoL when compared to euthyroidism group. A lower score in physical role functioning was found in both subgroups with active disease (hyperthyroidism and euthyroidism using thionamides). A lower score was also seen in visual function, only in patients with hyperthyroidism, without difference in appearance. No difference was found in cognition between patients. Younger ages at diagnosis, male sex, euthyroidism and absence of ophthalmopathy were factors associated with better QoL, as well as a shorter disease duration was associated with better recall, attention and calculation. CONCLUSIONS: An impairment in QoL among patients with active GD was evidenced, even in those receiving thionamides and in euthyroidism. Ophthalmopathy was a factor associated with a poor QoL and no clear evidence of cognitive impairment was demonstrated.

Association between subclinical thyroid dysfunction and depressive symptoms in the Korean adult population: The 2014 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Clinical hyper and hypothyroidism are associated with a risk for depression. OBJECTIVES: This study was performed to investigate the association between depressive symptoms and subclinical thyroid dysfunction. METHODS: Among the 7,550 subjects who participated in the 2014 Korea National Health and Nutrition Examination Survey, 1,763 participants without overt thyroid disease were included in this study. Serum thyroid stimulating hormone (TSH), serum free thyroxine (fT4), and depressive symptoms were analyzed based on the Patient Health Questionnaire (PHQ9). RESULTS: The percentages of subjects with subclinical hypothyroidism and subclinical hyperthyroidism were 3.3% and 2.6%, respectively. The percentages of subjects with moderate (10-14 points), moderately severe (15-19 points), and severe (≥20 points) depression according to the distribution of PHQ-9 scores were 4.7%, 1.1%, and 0.3%, respectively. TSH, fT4, and the percentage of patients with subclinical hypothyroidism were not significantly associated with PHQ-9 score. However, the percentage of patients with subclinical hyperthyroidism increased significantly with PHQ9 score (P = 0.002). Subjects with subclinical hyperthyroidism had higher PHQ-9 scores than those with normal thyroid function (mean ± standard error [SE], 4.2 ± 0.5 vs. 2.7 ± 0.1 points, P = 0.010). More subjects with subclinical hyperthyroidism had a PHQ9 score ≥ 10 than did those with normal thyroid function (mean ± SE, 17.1 ± 3.5 vs. 5.8 ± 0.6%, P = 0.005). We performed logistic regression analyses for the presence of depressive symptoms, using age, sex, education, household income, alcohol drinking, smoking, diabetes, cerebrovascular disease history, subclinical hypothyroidism, and subclinical hyperthyroidism as variables. Subclinical hyperthyroidism was associated with the presence of clinically relevant depression (PHQ9 score ≥ 10), (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.75-9.31; P = 0.001), and clinically significant depression (PHQ9 score ≥ 15), (OR, 7.05; 95% CI, 1.67-29.67; P = 0.008), respectively. However, subclinical hypothyroidism was not associated with the presence of clinically relevant depression (OR, 1.15; 95% CI, 0.39-3.38; P = 0.800), or clinically significant depression (OR, 3.35; 95% CI, 0.71-15.79; P = 0.127). CONCLUSIONS: We demonstrated that subclinical hyperthyroidism was independently associated with depressive symptoms in the Korean general population using national cross-sectional data.

Abnormal spontaneous brain activity is associated with impaired emotion and cognition in hyperthyroidism: A rs-fMRI study.

Hyperthyroid patients undergo emotional and cognitive dysfunction. However, the neurological basis for it remains ambiguous. Amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to investigate abnormal spontaneous activity in hyperthyroidism for the first time. 29 hyperthyroid patients and 29 healthy controls (HC) received 3.0T magnetic resonance imaging (MRI) scans and neuropsychological assessments. Compared with HC, hyperthyroid patients showed decreased ALFF in left medial frontal gyrus (MeFG) and left posterior cingulate cortex (PCC). Hyperthyroidism group exhibited decreased ReHo in left MeFG. Within hyperthyroidism group, ALFF values in left MeFG were positively correlated with Hamilton Anxiety Rating Scale (HARS) Z-scores, but negatively correlated with processing speed Z-scores. Besides, ALFF values in left precuneus had a positive correlation with HARS Z-scores. As a result, abnormal brain spontaneous activity mainly in default mode network (DMN) implicated the neuro-pathological substrate of relevant emotional and cognitive dysfunction in hyperthyroid patients.

Changes in Resting-State Cerebral Activity in Patients with Hyperthyroidism: A Short-Term Follow-Up Functional MR Imaging Study.

To investigate the brain functional abnormality of hyperthyroid patients before and after treatment for one month using resting-state functional magnetic resonance imaging (rs-fMRI). Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) analysis were performed in 27 new-onset untreated hyperthyroid patients relative to 30 healthy controls. In addition, follow-up data were available for 19 patients treated with methimazole for one month. Compared with healthy controls, patients exhibited lower ALFF in the right posterior cingulate cortex (PCC); increased FC in the bilateral anterior insula (AI), bilateral posterior insula (PI) and left anterior lobe of the cerebellum (ALC); and decreased FC in the bilateral lateral prefrontal cortex (LPFC), the right medial temporal gyrus (MTG) and the bilateral PCC. Compared with the hyperthyroid status, patients with improved thyroid function showed increased FC in the right LPFC and right dorsolateral prefrontal cortex (DLPFC). Subsequently, Pearson's correlation analyses were performed between abnormal ALFF, FC, neuropsychological assessment and serum free triiodothyronine (FT3) levels. The results indicated that the alterations in regional and network-level brain functions, which might underlie different psychiatric complications were dynamic and interactional processes in hyperthyroidism. Moreover, the improvement in regional brain FC was correlated with the efficacy of anti-thyroid medication.

A novel treatment for subclinical hyperthyroidism: a pilot study on the beneficial effects of l-carnitine and selenium.

OBJECTIVE: The definition itself of subclinical hyperthyroidism (SHyper) and, therefore, the therapeutic approach to patients with SHyper still remains undefined and controversial. Therefore, the interest of finding a novel and alternative therapy for SHyper has caught the attention. An observational pilot study was performed to assess the effects of l-carnitine and selenium in the management of SHyper symptoms and endocrine profile in patients affected by this disease. PATIENTS AND METHODS: Patients with TSH levels between 0.1-0.4 mIU/L and positive antibodies were recruited in this study. Subjects received orally one tablet containing 500 mg of l-carnitine and 83 mcg of selenium (L-Carn + Se), daily for 1 month. The primary outcome was the improvement of the quality of life (QoL) with the disappearance of main symptoms (subjective symptomatology) associated to SHyper, evaluated through a 9-items short form survey. Secondary outcomes included TSH, fT3, and fT4, TPOAb, TgAb measurement. Primary and secondary outcomes were evaluated at baseline, after the completion of treatment and after a successive month without treatment. RESULTS: After 1-month treatment, the subjective symptomatology significantly dropped from 25.61 ± 1.19 to 12.11 ± 1.15 (p < 0.05). On the other hand, during the following 1-month period without treatment, it increased back to 23.33 ± 1.35 (p < 0.05). Thyroid hormones and auto-antibodies remained in their normal range. CONCLUSIONS: The present pilot study has shown that L-Carn + Se significantly reduced symptoms associated with SHyper, improving QoL of patients, without significant modifications of their endocrine profile. In addition, it is noteworthy that the extension of treatment seems necessary to prevent symptoms reappearance. Prospective randomized controlled trials are needed to address clinicians to define the appropriate treatment-settings for this disorder.

Early neuropsychological adverse events after switching from PI/r to dolutegravir could be related to hyperthyroidism in patients under levothyroxine.

We report two patients who had taken levothyroxine at the same dose for several years and who had stable thyroid stimulating hormone (TSH) levels, and who developed clinical and biological hyperthyroidism following switch from ritonavir-boosted protease inhibitors (PIs) to dolutegravir-based HAART. Levothyroxine is metabolized by deiodination and glucuronidation and the induction of glucuronidation by ritonavir leads to an increased elimination of levothyroxine and a necessity of higher daily doses. Patients who switch from ritonavir-boosted PIs to antiretroviral drugs-based HAART with minimal drug-interaction such as dolutegravir, may require an adjustment in their dose of levothyroxine in order to prevent hyperthyroidism due to impaired elimination of levothyroxine without ritonavir.

Quality-of-Life Impairments Persist Six Months After Treatment of Graves' Hyperthyroidism and Toxic Nodular Goiter: A Prospective Cohort Study.

BACKGROUND: The treatment of hyperthyroidism is aimed at improving health-related quality of life (HRQoL) and reducing morbidity and mortality. However, few studies have used validated questionnaires to assess HRQoL prospectively in such patients. The purpose of this study was to assess the impact of hyperthyroidism and its treatment on HRQoL using validated disease-specific and generic questionnaires. METHODS: This prospective cohort study enrolled 88 patients with Graves' hyperthyroidism and 68 with toxic nodular goiter from endocrine outpatient clinics at two Danish university hospitals. The patients were treated with antithyroid drugs, radioactive iodine, or surgery. Disease-specific and generic HRQoL were assessed using the thyroid-related patient-reported outcome (ThyPRO) and the Medical Outcomes Study 36-item Short Form (SF-36), respectively, evaluated at baseline and six-month follow-up. The scores were compared with those from two general population samples who completed ThyPRO (n = 739) and SF-36 (n = 6638). RESULTS: Baseline scores for patients with Graves' hyperthyroidism and toxic nodular goiter were significantly worse than those for the general population scores on all comparable ThyPRO scales and all SF-36 scales and component summaries. ThyPRO scores improved significantly with treatment on all scales in Graves' hyperthyroidism and four scales in toxic nodular goiter, while SF-36 scores improved on five scales and both component summaries in Graves' hyperthyroidism and only one scale in toxic nodular goiter. In Graves' hyperthyroidism, large treatment effects were observed on three ThyPRO scales (Hyperthyroid Symptoms, Tiredness, Overall HRQoL) and moderate effects on three scales (Anxiety, Emotional Susceptibility, Impaired Daily Life), while moderate effects were seen in two ThyPRO scales in toxic nodular goiter (Anxiety, Overall HRQoL). However, significant disease-specific and generic HRQoL deficits persisted on multiple domains across both patient groups. CONCLUSIONS: Graves' hyperthyroidism and toxic nodular goiter cause severe disease-specific and generic HRQoL impairments, and HRQoL deficits persist in both patient groups six months after treatment. These data have the potential to improve communication between physicians and patients by offering realistic estimates of expected HRQoL impairments and treatment effects. Future studies should identify risk factors for persistent HRQoL deficits, compare HRQoL effects of the various therapies, and thereby aid in determining the optimal treatment strategies.

Is thyroid status associated with cognitive impairment in elderly patients in China?

BACKGROUND: The relationship between alterations in thyroid function and cognitive deficits has been investigated in several previous studies. Hypo-or hyperthyroidism and, to a lesser extent, subclinical thyroid dysfunction can negatively affect cognitive performance. However, limited data are available on the potential association of thyroid function with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the elderly Chinese population. METHODS: In the present study focusing on a population of elderly Chinese individuals ≥ 50 years of age, 77 cognitively normal controls, 64 patients with MCI, and 154 patients diagnosed with AD underwent assessment of thyroid status using thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels as variables. Cognitive function was evaluated with the aid of comprehensive neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Memory and Executive Screening (MES). RESULTS: Overall, 88.1 % of the subjects displayed normal thyroid function, 4.7 % were diagnosed with clinical hypothyroidism, 3.1 % with subclinical hypothyroidism, and 4.1 % with subclinical hyperthyroidism. After adjusting for covariates (age, sex, education years and body mass index), no association was evident between mild cognitive impairment or AD and thyroid dysfunction. However, lower serum TSH was correlated with risk of AD (odds ratio [OR]: 2.78, 95 % confidence interval [95% CI]: 1.11-6.99). CONCLUSION: Neither hypothyroidism nor subclinical hyperthyroidism was associated with AD and MCI in this population-based elderly Chinese cohort. Our findings need to be confirmed in a longitudinal study.