Health Status, Psychological Symptoms, Mood, and Cognition in L-Thyroxine-Treated Hypothyroid Subjects

Division of Endocrinology, Diabetes & Clinical Nutrition, Oregon Health and Science University, Portland, Oregon, United States
Thyroid (Impact Factor: 4.49). 04/2007; 17(3):249-58. DOI: 10.1089/thy.2006.0252
Source: PubMed

ABSTRACT Many hypothyroid subjects receiving L-thyroxine (L-T4) complain of psychological symptoms or cognitive dysfunction. However, there is limited validated information on these self-reports.
Cross-sectional comparison of 20 euthyroid and 34 treated hypothyroid subjects, aged 20-45 years, with normal thyroid-stimulating hormone (TSH) levels. Subjects underwent the following validated measures: Short Form 36 (SF-36); Symptom Checklist 90-Revised (SCL-90-R); Profile of Mood States (POMS); and tests of declarative memory (Paragraph Recall, Complex Figure), working memory (N-Back, Subject Ordered Pointing, Digit Span Backwards), and motor learning (Pursuit Rotor).
L-T4-treated subjects had higher mean TSH and free T4 levels, but free triiodothyronine (T3) levels were comparable to controls. L-T4-treated subjects had decrements on SF-36 and SCL-90-R summary scales and subscales. These subjects performed slightly worse on N-Back and Pursuit Rotor tests. Neither TSH nor thyroid hormone levels were associated with performance on psychological or cognitive measures.
This group of L-T4-treated subjects had decrements in health status, psychological function, working memory, and motor learning compared to euthyroid controls. Higher mean TSH levels suggest this may be related to suboptimal treatment, although there were no correlations between TSH levels and outcomes. These findings are limited by potential selection bias, and randomized studies targeting different TSH levels and memory subdomains would clarify these issues.

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    • "Studies also show that thyroid hormones continue to modulate the function of the adult brain, which explains the tight regulation of thyroid hormone transport into the brain, regionspecific T 4 to T 3 conversion as well as T 3 receptor levels (Ceballos et al., 2009). Epidemiological studies indicated that thyroid dysfunction whether hypothyroidism or hyperthyroidism (overt or subclinical) increases the risk of cognitive impairment, (Beydoun et al., 2013; Bono et al., 2004; Correia et al., 2009; Miller et al., 2006; Munte et al., 2001) although the evidence is still sparse (Almeida et al., 2007; Ceresini et al., 2009; de Jongh et al., 2011; Formiga et al., 2014; Joffe et al., 2013; Kramer et al., 2009; Parle et al., 2010; Samuels et al., 2007; Wijsman et al., 2013). It is less well-known how thyroid hormone fluctuations within normal ranges can affect cognitive outcomes in the general population, particularly when studies have examined cognitive performance among middle-aged adults (Beydoun et al., 2012, 2013; Grigorova and Sherwin, 2012; van Boxtel et al., 2004). "
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    ABSTRACT: Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. We investigated associations between thyroid hormones and longitudinal cognitive change, within and outside of reference ranges, stratifying by sex and race. This longitudinal study used data from the Healthy Aging in Neighborhoods of Diversity Across the Lifespan study, set in Baltimore City, MD, 2004-2013, on adults aged 30-64 years at baseline visit, with a length of follow-up between visits 1 and 2 ranging from <1 to 8 years; mean ± standard deviation: 4.64 ± 0.93. The final analytic sample sizes ranged from 1486 to 1602 participants with 1.6-1.7 visits per participant (total visits: 2496-2757), depending on the cognitive test. Eleven cognitive test scores spanning domains of learning or memory, language or verbal, attention, visuospatial and/or visuoconstruction, psychomotor speed, executive function, and mental status were used. Mixed-effects regression models were conducted, interacting time of follow-up with several thyroid exposures. Whites performed better than African Americans, with only 4 cognitive test scores of 11 declining significantly over time. Importantly, above reference range thyroid stimulating hormone (vs. reference range, thyroid stimulating hormone, above reference range [TSHarr]) was linked to faster rates of decline on the digits span backwards test, reflecting working memory (TSHarr × time γ ± standard error: -0.14 ± 0.05, p = 0.006) and clock-command, at test of visuospatial and/or visuoconstruction abilities (TSHarr × Time γ ± standard error: -0.10 ± 0.04, p = 0.004). The latter finding was replicated when comparing normal thyroid function to "subclinical hypothyroidism". Within-reference ranges, a higher thyroid stimulating hormone was related to faster decline on the clock-command test scores in women. In sum, higher baseline thyroid stimulating hormone was associated with faster cognitive decline over-time among urban US adults, specifically in domains of working memory and visuospatial and/or visuoconstruction abilities. Published by Elsevier Inc.
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    • "Groups were additionally matched for handedness (one left per group), smoking status (three smokers per group) and use of estrogen containing contraceptives (five patients, six control subjects). All subsequent analyses were controlled for age, sex, TSH, fT3 and fT4 to ensure ideal matching for biochemical thyroid status (Samuels et al., 2007). Analyses were repeated with control for age and sex alone to investigate group differences under the influence of differences in biochemical status between treated and healthy participants. "
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    Psychoneuroendocrinology 04/2014; 42:188–198. DOI:10.1016/j.psyneuen.2014.01.015 · 4.94 Impact Factor
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    • "Levothyroxin (thyroxin) replacement therapy improves memory in subclinical hypothyroid subjects (Osterweil et al., 1992; Monzani et al., 1993; Baldini et al., 1997; Jensovsky et al., 2002). However, clinical reports show variable results as to whether the thyroid hormone replacement therapy fully restores the hypothyroidism-induced impaired learning and memory (Treadway et al., 1967; Jaeschke et al., 1996; Capet et al., 2000; Miller et al., 2006; but see Mennemeier et al., 1993; Leentjens and Kappers, 1995; Wekking et al., 2005; Samuels et al., 2007b). While a large body of literature is available on the effect of thyroid hormone deficiency during the developmental stage (e.g. "
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