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Institute of Clinical Medicine (R.J., K.W.), University of Tromsø, 9037 Tromsø, Norway; Departments of Internal Medicine (H.S., A.N.) and Clinical Chemistry (J.S.), University Hospital of North Norway, 9038 Tromsø, Norway; and Department of Nephrology (T.G.J.), National Hospital, 0027 Oslo, Norway
Address all correspondence and requests for reprints to: Rolf Jorde, Medical Department B, University Hospital of North Norway, 9038 Tromsø, Norway. E-mail: rolf.jorde{at}unn.no.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Subjects: A total of 89 subjects (45 males) with SHT and 154 control subjects (72 males) were recruited from a general health survey (the fifth Tromsø study). Sixty-nine of those with SHT were included in a placebo-controlled, double-blind intervention study with T4 medication for 1 yr.
Main Outcome Measures: We used fourteen tests of cognitive function, Beck Depression Inventory, General Health Questionnaire, and a questionnaire on hypothyroid symptoms.
Results: The mean ± SD serum TSH in the SHT and control group were 5.57 ± 1.68 and 1.79 ± 0.69 mIU/liter, respectively. There were no significant differences in cognitive function and hypothyroid symptoms between the two groups, but those with SHT scored significantly better than the controls on the GHQ-30. At the end of the intervention study, serum TSH in the T4 group (n = 36) and the placebo group (n = 33) were 1.52 ± 1.51 and 5.42 ± 1.96 mIU/liter, respectively. T4 substitution had no effect on any of the parameters measured.
Conclusion: In subjects with SHT where the serum TSH level is in the 3.5–10.0 mIU/liter range, there is no neuropsychological dysfunction, and compared with healthy controls, there is no difference in symptoms related to hypothyroidism.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The effect of T4 supplementation in SHT has been most thoroughly studied regarding the lipid profile, and there appears to be a slight effect on serum total and low-density lipoprotein cholesterol levels (9). However, studies regarding effects of T4 supplementation on clinical symptoms and neuropsychological dysfunction in SHT are less conclusive with reports showing a clear positive effect (10, 11), a moderate or no effect (12), and even an adverse effect (13).
By definition, subjects with SHT should not have overt symptoms of hypothyroidism. However, because the disease usually develops gradually, the symptoms may go unrecognized by the patients and their families. Symptoms compatible with hypothyroidism are also seen in subjects with normal thyroid function (14), and accordingly, the presence of such symptoms in subjects with SHT may have causes other than thyroid dysfunction. Many patients are therefore diagnosed with SHT because thyroid function tests are often performed in subjects with nonspecific symptoms such as fatigue and depression. Therefore, to assess the true association between reduced thyroid function and symptoms, which may be of importance in the discussion on treatment with T4, one should not include subjects recruited from clinical practice. In addition, the subjects should not be aware of their thyroid status before testing.
We recently had the opportunity to study such a group. Thus, the Tromsø study, which is an epidemiological health survey, was performed for the fifth time in 2001, and serum TSH was measured in 7954 subjects. From this cohort, subjects with SHT and normal controls were recruited and examined with a broad range of neuropsychological tests and symptom scores. To study a group of subjects where the thyroid function was only moderately reduced, we included subjects with serum TSH in the range of 3.5–10.0 mIU/liter.
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Subjects and Methods |
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Subjects with serum TSH level between 3.5 and 10.0 mIU/liter were invited to a follow-up examination at the Clinical Research Unit at the University Hospital of Tromsø. Those who reported a history of coronary infarction, angina pectoris, or stroke in the questionnaire, those participating in other follow-up studies, those using thyroid medication, and those above the age of 80 were not invited. The hospital records were also reviewed to exclude subjects with serious diseases not reported in the questionnaire. For each subject with serum TSH between 3.5 and 10.0 mIU/liter, a randomly selected age- and sex-matched control subject from the fifth Tromsø study with serum TSH in the range 0.50–3.49 mIU/liter was also invited. The invitation letter informed about the purpose of the study but did not disclose the subject’s TSH status.
At the follow-up visit, blood was drawn in the nonfasting state and serum samples analyzed for TSH, free T4, and free T3. A clinical examination was performed, height and weight were measured in light clothing wearing no shoes, and body mass index (BMI) was calculated as weight (kg) divided by squared height (m2). A questionnaire focusing on hypothyroid symptoms was administered. Those who still had serum TSH between 3.5 and 10.0 mIU/liter and with free T4 and free T3 within the reference range, and without obvious clinical symptoms of hypothyroidism, were considered to have SHT. They were informed that their thyroid status was similar to that at the Tromsø study and invited to additional examinations. The control subjects who at the follow-up visit still had serum TSH within the 0.50–3.49 mIU/liter range and with normal serum free T4 and free T3 were similarly informed that their thyroid status was unchanged and invited to additional examinations. Those consenting were, on a separate day, in the nonfasting state, examined with neuropsychological tests for cognitive and emotional function. The tests were administered in two sessions on the same day, each lasting 1 or 2 h and separated by a coffee break. The examiners, who were nurses extensively trained and certified by a clinical neuropsychologist (K.W.) and an experienced technician, carried out the tests in a standardized fashion and in the same order. The examiners were blinded to the TSH status of the participants.
The subjects were then informed about their thyroid status. Those with SHT were invited to a 12-month intervention study. Those willing were randomized to placebo or T4. The T4 tablets were in 25-, 50-, and 100-µg doses, and the corresponding placebo tablets were identical looking. Each subject was to take three tablets every day, and by combining T4 and placebo tablets, daily doses of T4 could be 25, 50, 75, 100, 125, 150, or 175 µg. During the first 6 wk, all subjects in the T4 group were given 50 µg daily, and for the following 6 wk 100 µg daily. Thereafter, the T4 dose was given according to the TSH levels, aiming at a level between 0.5 and 1.5 mIU/liter using the following algorithm: serum TSH less than 0.50 mIU/liter and free T4 more than 29 pmol/liter, reduce T4 dose by 50 µg; serum TSH less than 0.50 mIU/liter and free T4 less than 30 pmol/liter: reduce T4 dose by 25 µg; serum TSH 0.50–1.50 mIU/liter, unchanged T4 dose; serum TSH 1.51–4.00 mIU/liter, increase T4 dose by 25 µg; serum TSH more than 4.00 mIU/liter, increase T4 dose by 50 µg (if good compliance).
Nonfasting blood samples for serum TSH, free T4, and free T3 were drawn after 3, 6, 9, and 12 months. On the blood sampling days, the T4 or placebo tablets were taken after the blood sampling. The TSH results were available after 1 or 2 d, and T4 (or placebo) tablets for the next 3-month period were sent by mail. The subjects continued their previous dose until they received the new tablets. At each visit, unused tablets from the previous period were counted. The compliance rate was calculated as number of tablets not returned divided by the corresponding number of days. After 12 months, a questionnaire focusing on change in symptoms since the first visit was administered and the neuropsychological tests repeated.
Tests of cognitive function
For attention, sustained attention, and working memory, we used the Digit Span forward and backward test (subtests from Wechsler Memory Scale-Revised) (17) and the Seashore Rhythm test from the Halstead-Reitan test battery (18).
For psychomotor/cognitive speed, we used the Trail Making test, part A (18); the Stroop Color-Word test, parts 1 and 2 (reading speed) (scores for 1 and 2 added together) (19), modified version (20); and the Digit Symbol test (21).
For memory, we used the verbal and visual paired associates immediate and 30-min delayed recall (from Wechsler Memory Scale-Revised) (17) and verbal recall test and a word list consisting of 12 words, a subtest from California Verbal Learning Test (22).
For language/word fluency, we used the Controlled Oral Word Association test with words beginning with the letters F, A, and S (23).
For cognitive flexibility/executive function, we used the Trail Making test, part B (18), and the Stroop Color-Word test, part 3 (color-word interference effect) (19, 20).
For speed of information processing, we used the California Computerized Assessment Package (CalCAP) (24).
For intelligence, we used the subtest Vocabulary from the Wechsler Adult Intelligence Scale (WAIS) (21).
A composite score for cognitive function was made by adding together the Z-scores for the following seven tests: Digit Span forward, Digit Span backward, Stroop test parts 1 and 2 (scores added together), Digit Symbol test, verbal recall, visual recall, and Stroop test part 3. If a negative score was favorable, the Z-score was multiplied by –1.
Tests of emotional function
Depressed mood was measured with the Beck Depression Inventory (BDI), which is a self-completed questionnaire of 21 items in multiple-choice format (25). The items constituting the BDI have been divided into two subscales. The first, Cognitive-Affective, assesses the mental aspect of depression (items 1–13). The second, Somatic-Vegetative, measures vegetative and somatic symptoms (items 14–21). For the BDI, the total score and the subscale scores were obtained for each patient.
Mental health status (or psychological distress) was assessed by the General Health Questionnaire (GHQ), which is a generic health instrument and may thus be applied across different diseases or conditions (26). The GHQ comes in several versions, and we applied the GHQ-30 version. On each of the 30 items, subjects are asked to compare their perceived state of health with four standard answers in the questionnaire. If scored according to the GHQ-scoring method (0 – 0 – 1 – 1), it may be used as a screening instrument identifying cases with nonpsychotic psychiatric disturbances or as a measure of psychiatric disturbance in the population. Because the objective of this study was not to identify cases but to obtain quantitative measures of well-being and mental health, we applied the Likert-scoring method (0 – 1 – 2 – 3), which also allows factor-scoring within the five subscales of GHQ-30. These factors are identified as factor A (anxiety), factor B (feelings of incompetence), factor C (depression, hopelessness), factor D (difficulty in coping), and factor E (social dysfunction) (27).
Symptom score
A questionnaire containing 19 questions related to hypothyroid symptoms was administered at inclusion. A total symptom score was created by adding together the number of present symptoms (28). At the end of the study, a similar questionnaire with 10 questions on change of symptoms was administered, and a change score was calculated, giving 1 point if the change was in the better (more euthyroid) direction, –1 point if the change was in the hypothyroid direction, and 0 point if there was no change.
Laboratory analyses
Serum TSH levels from the fifth Tromsø study and the study on the SHT and control groups were analyzed with the Modular E instrument (Hoffmann-La Roche, Basel, Switzerland) with reference range 0.2–4.0 mIU/liter. Accordingly, the values from this assay were used when including the subjects. At the start of the intervention study, our Department of Clinical Chemistry changed to the AxSYM (Abbott, IL) instrument with inherent reagents. Because we knew about this change in advance, serum samples from the SHT/control group study were stored and later analyzed with the new assay. All serum TSH, free T4, and free T3 values presented therefore represent analysis on the AxSYM instrument with reference values 0.20–4.20 mIU/liter, 9–22 pmol/liter, and 2.8–7.1 pmol/liter, respectively.
Statistical analyses
Normal distribution was evaluated with determination of skewness and kurtosis and visual inspection of histograms. The scores for tests of cognitive function were considered normally distributed except for Seashore Rhythm test, Trail Making B, Stroop Color-Word test parts 1 and 2, and the Stroop Color-Word test part 3. After logarithmic transformation, these latter variables assumed normal distribution and were applied as such when used as dependent variables.
To test for interactions, factor analyses with scores for cognitive function as dependent variables; TSH group (SHT or control), gender, smoking status (current smoker/nonsmoker) as factors; and age and BMI as covariables were performed. This revealed significant effects of smoking status as well as interactions between smoking status and TSH group regarding several of the tests for cognitive function, and additional analyses regarding cognitive function were therefore done in nonsmokers only because there were too few smokers to allow significant relations to be found in that group.
None of the tests for emotional function were normally distributed, nor did they assume normal distribution after logarithmic transformation. When compared with the Mann-Whitney U test in the control and the SHT groups separately, smokers and nonsmokers did not differ significantly on any of the tests for emotional function [P = 0.07 for GHQ-E (social dysfunction) in the SHT group; all other P values > 0.33]. Similarly, the symptom scores were not normally distributed, and there were no significant effects of smoking status when tested as above. Smokers and nonsmokers were therefore evaluated together regarding emotional function and symptom scores, but the results are also given for the nonsmokers separately.
Cognitive function was compared between the two groups with Student’s t test and also with a general linear model with the parameter in question as dependent variable and with TSH group (SHT or control) and gender as factors and age and BMI as independent variables. A multiple linear regression model was used to assess independent predictors of the test scores for cognitive function. Because of the high correlation between free T4 and free T3, two models were used, with gender, age, BMI, serum TSH, and serum free T4 (or serum free T3) as covariables.
For emotional function and the symptom scores, the SHT group and the controls, and the males and the females, were compared with the Mann-Whitney U test. The Kruskal-Wallis test was used to evaluate other predictors of emotional function and symptom scores. For this purpose, the subjects were divided into age, BMI, TSH, free T4, and free T3 quartiles. The Mann-Whitney U test was used as post hoc test between the lowest and the highest quartiles.
The main analyses were done comparing the SHT group with TSH range 3.5–10.0 mIU/liter with the controls, but in addition, those in the SHT group with serum TSH in the range 5.0–10.0 mIU/liter were also compared separately with the control group.
In the intervention study, comparisons between the T4 and placebo groups at the start and end of the intervention were done similarly as between the SHT group and the controls. In addition, 
values (value at end of intervention minus value at inclusion) were compared between the two groups with similar statistics. Correlations were evaluated with the Pearson correlation coefficient.
Unless otherwise stated, all data are expressed as mean ± SD. All tests were done two-sided, and P < 0.05 was considered statistically significant. Corrections for multiple comparisons were not performed. Statistical analyses were performed with SPSS version 11.0 (SPSS Inc., Chicago, IL).
Ethics
The Regional Ethics Committee approved the study, and all participants gave their written informed consent.
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Results |
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There were no significant differences between the SHT group and the controls on any of the individual tests or on the composite score for cognitive function (Table 2). In the multiple linear regression model, age was the most important (and negative) predictor of cognitive performance. The serum TSH level was significantly and negatively associated with performance on the Trail Making test A; the serum free T4 level was significantly and positively associated with performance on the Stroop test parts 1 and 2 and the word association test; whereas the serum free T3 level was significantly and negatively associated with performance at the visual recall test (Table 3). There was no significant association between serum TSH, free T4, or free T3 and the composite score for cognitive function (Table 3).
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Those with SHT had a significantly more favorable score than the controls on the GHQ-30 test (P = 0.006, Mann-Whitney U test) (Table 4). There was an almost significant difference between males and females on the GHQ-30 test (1.6 ± 3.1 and 2.5 ± 4.2, respectively, P = 0.07, Mann-Whitney U test). Therefore, the GHQ-30 scores in the SHT and control group were compared in males and females separately [1.0 ± 2.1 vs. 1.9 ± 3.5 (P = 0.03) in males and 1.2 ± 2.0 vs. 3.2 ± 4.9 in females (P = 0.06), respectively, Mann-Whitney U test]. When the cohort was divided into serum TSH quartiles, there was a significant association between serum TSH and the GHQ-30 score (P = 0.03, Kruskal-Wallis test). The GHQ-30 score in the lowest and highest serum TSH quartiles were 3.4 ± 5.4 and 1.4 ± 2.4, respectively (P = 0.05, Mann-Whitney U test). Also, when evaluating nonsmokers separately, there was a significant difference between the SHT and control group regarding the GHQ-30 test (Table 4).
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Questionnaire on hypothyroid symptoms
Except for a single question ("Are you more tired than before?") where those in the SHT group with serum TSH in the range 5.0–10.0 mIU/liter scored significantly more favorably than the controls, the SHT group and the controls did not differ significantly on any of the questions on hypothyroid symptoms or on the total symptom score (Table 5). Examining the nonsmokers separately did not add additional information. There was no significant relation between quartiles of serum TSH, free T4, or free T3 and the total symptom score when evaluated with the Kruskal-Wallis test.
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Thirty-six subjects were included in the T4 group and 34 subjects in the placebo group. One subject in the placebo group dropped out after 6 months because of serious disease unrelated to thyroid function and was excluded from analyses in the intervention study. Characteristics of the subjects are given in Table 1
. In the T4 group, one subject had serum TSH less than 0.05 mIU/liter, nine subjects had 0.05–0.48 mIU/liter, nine subjects had 0.53–1.37 mIU/liter, nine subjects had 1.52–1.93 mIU/liter, four subjects had 2.17–2.74 mIU/liter, and four subjects had 3.75–6.85 mIU/liter at the end of the study. The compliance rate in the T4 group and the placebo group for the entire study was 0.91 ± 0.06 in both groups. There was a significant and negative correlation between compliance rate the first 3 months and serum TSH at the 3-month visit (r = –0.40; P = 0.017) but not at later intervals. The thyroid status, T4 use, and compliance during the intervention study are given in Table 6.
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), emotional function (Table 7), or hypothyroid symptoms (Table 8) between the T4 and the placebo group, either at the start of the intervention or at the end of the study. The symptom score at the end of the study (10 questions on change of symptom) were –0.08 ± 2.23 and –0.65 ± 2.04 in the T4 and placebo groups, respectively. Furthermore, when evaluating values (scores at the end of study minus scores at the start), there were no significant differences regarding cognitive or emotional function, whereas on one of the individual questions regarding change in hypothyroid symptoms ("Are your clothes looser/no change/tighter than one year before?"), those given T4 scored significantly more in the positive direction (clothes looser) than the placebo group (Table 8). There was no relation between these values and serum TSH, free T4, and free T3, either when looking at all 69 subjects in the intervention study together or when analyzing those given T4 and those given placebo separately.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In the SHT group, we included subjects with serum TSH 3.5–10.0 mIU/liter, which is a lower range than what has been used in most other studies. However, the upper normal TSH level is a matter of definition and depends on whether subjects with presence of thyroid autoantibodies and other risk factors for hypothyroidism are included or not. Thus, in the study by Bjøro et al. (29) the upper normal serum TSH level was approximately 3.5 mIU/liter if excluding those with thyroid autoantibodies, and in the NHANES III study (30) the TSH 97.5 percentile was reduced from 5.80 mIU/liter in the total population to 4.12 mIU/liter if excluding those with thyroid autoantibodies and other risk factors.
Cognitive symptoms such as slow mentation, reduced memory function, and inability to concentrate are frequently reported in subjects with overt hypothyroidism (31, 32) and also in some studies on SHT. Thus, impaired memory function in SHT was found by Baldini et al. (33), del Ser Quijano et al. (34), and Monzani et al. (10). In the latter study, 14 subjects with SHT were compared with 50 control subjects. There was a significant impairment in memory in the SHT group and a significant improvement after treatment with T4. However, their group of SHT subjects had a mean serum TSH of 8.8 mIU/liter, which was considerably higher than in our study. Similarly, Jaeschke et al. (12) found T4 treatment to significantly improve a composite psychometric memory score in SHT, but their mean serum TSH level was 12.1 mIU/liter, which in this context is rather high.
In our study, we applied a broad range of tests of cognitive function. On 11 of the 14 tests, the control subjects scored slightly better than the SHT group, and they also had a better composite cognitive function score. However, none of the differences were statistically significant. Furthermore, in the multiple linear regression model, the direction of the association between serum TSH and cognitive function was in favor of a low serum TSH in only six of the 14 tests, and on only one of these six tests (the Trail Making A test) was the association statistically significant. Because we did not do a Bonferroni or other correction for multiple testing, this significance could well be the result of chance. Accordingly, cognitive function was not markedly affected in our SHT group, probably because their serum TSH levels were not raised above 10 mIU/liter.
Similar to cognitive function, there is an association between overt hypothyroidism and depression (35). Depressive features are also reported more frequently in SHT with slight improvement after T4 treatment (10, 36). However, in a large epidemiological study by Pop et al. (37), depression was only weakly and nonsignificantly associated with SHT, and in our study the subjects with SHT actually had a better score on the BDI than the controls. Furthermore, in our study those with SHT had a significantly better score than the controls on the GHQ-30. When evaluated with the Likert-scoring method, this trend was also seen for each of the five subfactors anxiety, feeling of incompetence, depression, difficulty in coping, and social dysfunction.
The classical signs of hypothyroidism are well known, and symptom scores have been developed that clearly discriminates between euthyroid and hypothyroid subjects (38, 39). The number of symptoms correlate with degree of hypothyroidism (38, 39), which was also demonstrated in the large epidemiological Colorado Thyroid Disease Prevalence Study (40) that included 25,862 subjects voluntarily attending a health fair. Among the 2336 subjects classified as SHT (including 269 subjects taking T4), the percentage of subjects reporting symptoms associated with hypothyroidism was slightly but significantly higher than in the euthyroid group (13.7 vs. 12.1%) (40). Furthermore, in a study of 63 patients with SHT treated with T4 or placebo by Meier et al. (11), those given T4 had a significant improvement in symptom score as compared with baseline values. However, the change in symptoms over the 48-wk treatment period between the placebo group and the T4 group did not differ significantly, and the improvement in symptom score was seen in those that had serum TSH higher than 12 mIU/liter before the start of T4 treatment. In accordance with this, because we included only subjects in the SHT group that had serum TSH between 3.5 and 10.0 mIU/liter, there was no difference between the SHT and control group regarding symptoms in our study.
In addition to the comparison between the SHT and control group, we also performed a double-blind placebo-controlled intervention study with T4 for 1 yr. Because we did not find any significant differences between the SHT group and the controls (except for GHQ-30), it was no surprise that intervention with T4 had no effect on cognitive function or depression and that most of the subjects thought they had received placebo. Furthermore, there was no negative effect on the GHQ-30 score by T4 substitution, which does bring into question the importance of our finding of a difference between the SHT and control group regarding this score.
We tried to tailor the T4 dose in steps of 25 µg to achieve a serum TSH between 0.5 and 1.5 mIU/liter. However, despite acceptable compliance and strict adherence to a dosage algorithm designed to reach this target, and serum TSH measurement and dose adjustment every third month, the treatment goal was reached only in nine of the 36 subjects. This illustrates that a target range of 0.50–1.50 mIU/liter probably is too narrow and that T4 doses may need to be titrated in smaller steps than 25 µg per day. However, there was no relation between change in serum TSH in the intervention group and any of the parameters measured, and because the average serum TSH was 1.52 mIU/liter at the end of the intervention, we feel it is unlikely that a slightly higher average T4 dose would have significantly affected the neuropsychological test scores.
Our study has several weaknesses. We cannot rule out that we would have found significant differences between the SHT and the control group had we included more subjects. However, to include 89 subjects with SHT, we had to screen almost 8000 subjects, and a larger group would be hard to find. Furthermore, including subjects from an epidemiological survey would exclude those whose hypothyroid symptoms had made them seek medical help leading to T4 treatment. Accordingly, the true prevalence of symptoms and dysfunction related to serum TSH in the range 3.5–10.0 mIU/liter and with free T4 and free T3 within the reference range, is probably higher than that found by us. Furthermore, our SHT patients had a mean TSH level of 5.5 mIU/liter, and our results do not necessarily apply to those with higher serum TSH levels. However, when looking separately at those with serum TSH in the range 5.0–10.0 mIU/liter, there was no trend toward a difference between these SHT subjects and the controls. The subjects were not informed about their thyroid status when they were invited, but they knew that the focus of the study was thyroid dysfunction. Because only 66% of those invited to the follow-up examination attended, we cannot rule out a selection basis favoring those with symptoms compatible with thyroid disease. In addition, we excluded a considerable number of subjects because of concomitant diseases, and our results do therefore mostly apply to a fairly healthy population. The SHT and control groups were well matched regarding age and gender. However, there were significantly more smokers in the control group than in the SHT group. This could possibly be explained by the TSH-lowering effect of smoking (41), which would reduce the number of smokers with TSH values slightly above our 3.5 mIU/liter limit. Because of this difference in number of smokers, and the interactions between smoking and TSH status regarding cognitive function, subanalyses in nonsmokers were done on all tests. However, the number of smokers was too small to analyze these subjects separately, and we cannot exclude an effect of SHT on neuropsychological function in these subjects. In the intervention study, the mean serum TSH after 1 yr in those given T4 was 1.52 mIU/liter, which was approximately 0.5 mIU/liter above the target level. However, this is lower than in most other studies on the effects of T4 on neuropsychological function and symptoms (11, 12, 13), and we find it unlikely that a higher dose of T4 would have disclosed differences between those treated and those not.
On the other hand, our study has considerable strength. We applied a broad range of tests and used strict selection criteria for both SHT and control subjects. Those included were recruited from an epidemiological survey and not from clinical practice, which would have favored inclusion of subjects with symptoms unrelated to thyroid diseases. Our subjects also had a stable thyroid function because the serum TSH level was elevated (or normal) on at least two occasions before inclusion in the study. These points on inclusion criteria for SHT subjects in clinical trials have recently been emphasized in a commentary by Biondi et al. (42). Furthermore, we had a serum TSH level of 10.0 mIU/liter as the upper limit for inclusion in the SHT group. Patients with higher TSH levels may well have subclinical disease, but most of these patients will be started on treatment regardless of symptoms. Finally, although it could be considered a weakness that our patients had SHT with serum TSH in the narrow range 3.5–10 mIU/liter, this is also a strength of the study and shows that, at least with regard to cognitive and emotional function, there is no need to start treatment because of a slightly elevated serum TSH level.
In conclusion, in subjects whose serum TSH levels are not raised above 10 mIU/liter, as in our study, there are hardly any symptoms or neuropsychological dysfunctions.
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Acknowledgments |
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Footnotes |
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First Published Online November 1, 2005
Abbreviations: BDI, Beck Depression Inventory; BMI, body mass index; CalCAP, California Computerized Assessment Package; GHQ, General Health Questionnaire; SHT, subclinical hypothyroidism; WAIS, Wechsler Adult Intelligence Scale.
Received August 8, 2005.
Accepted October 25, 2005.
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S. Razvi, L. Ingoe, G. Keeka, C. Oates, C. McMillan, and J. U. Weaver The Beneficial Effect of L-Thyroxine on Cardiovascular Risk Factors, Endothelial Function, and Quality of Life in Subclinical Hypothyroidism: Randomized, Crossover Trial J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1715 - 1723. [Abstract] [Full Text] [PDF]
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 L. M. Roberts, H. Pattison, A. Roalfe, J. Franklyn, S. Wilson, F.D. R. Hobbs, and J. V. Parle Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med, October 17, 2006; 145(8): 573 - 581. [Abstract] [Full Text] [PDF]
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