Subclinical Thyroid Disease and Psychiatric Symptoms

I saw an interesting item in a recent issue of AMA MorningRounds which cited a New York Times article about the connection between subclinical thyroid disease and psychiatric symptoms and disorders.

It’s a fascinating article, especially the claim that one physician made about treating stage fright with thyroid hormone. I could not find one article in PubMed about this and a Google search only turned up the NY Times article itself. I would think that treating stage fright with thyroid hormone would make it worse since the side effects of thyroid replacement hormone can be anxiety, headache, sweating, heart palpitations, shortness of breath, chest pain, trembling, weight loss, and diarrhea.

The connection between subclinical thyroid disease and psychiatric illness has been a subject of controversy. On the one hand, few health professionals would disagree that a thyroid stimulating hormone level in excess of 10 (just as  the NY Times articles states) might contribute to symptoms of a mood disorder. And the “chicken and egg” analogies are commonly cited as reasons to doubt the origin of psychiatric symptoms in the setting of marginally abnormal thyroid hormone blood levels.

Excerpts from the book  I co-edited with Dr. Robert G. Robinson [1]:

Subclinical hypothyroidism affects about 5% of the general population and 15% of elderly
women. Common physical manifestations of hypothyroidism include fatigue, weight gain,
edema of the face and hands, paresthesias, cold intolerance, constipation, excessive sleepiness,
metromenorrhagia, anemia, and hoarseness. Signs may include bradycardia, dry skin,
and slowed reflexes. Psychiatric features include depression, dementia,mania, and hallucinations.
Before the advent of effective treatment,many patients presented with myxedema madness, marked by paranoid delusions and marked cognitive impairment. Nowadays, between 5% and 15% present with psychosis. Hypothyroidism frequently appears in patients presenting with rapid cycling bipolar disorder. Lithium is known to cause clinical hypothyroidism, but one study found it in far fewer non–rapid cycling bipolar patients with hypothyroidism in the context of lithium treatment than in rapid cyclers.

Hyperthyroidism is marked by low TSH and high serum T4 or T3; the subclinical form is defined by low TSH but normal T4 and T3.

Major causes of hyperthyroidism include Graves’ disease, toxic multi-nodular goiter, and toxic adenomas. However hyperthyroidism can also be caused by ingestion of high levels of thyroid hormone or secretion of thyroid hormone from an ectopic site.The most common clinical manifestations of hyperthyroidism are irritability, emotional lability, restlessness, fatigue, tremor, weight loss, palpitations, insomnia, and anxiety. Typical signs include eye stare, lid lag, warm smooth skin, goiter, tachycardia, fine tremor, atrial fibrillation, and brisk reflexes. Untreated, the patient can progress to suffer from psychosis and cognitive impairment. Although anxiety disorders dominate the psychiatric presentation, apathetic hyperthyroidism presents with depression, apathy, somnolence, and pseudodementia in the absence of the usual signs and symptoms of hyperthyroidism. Apathetic hyperthyroidism is more common in the elderly, although it has been described in younger patients. An acute delirium called Hashimoto’s encephalopathy (chronic autoimmune thyroiditis) can occur. True mania, marked by grandiosity, racing thoughts, and pressured speech, is much less commonly observed.

The excerpt about hyperthyroidism describes symptoms and signs that would not generally be seen in subclinical disease states.

The suggestion in the NY Times article that subclinical thyroid disease is intriguing. One representative study not mentioned was published in October of 2011, and the conclusion was that there was no effect of subclinical thyroid disorders on mental or physical function in older persons [2].

Another study published in November of 2011 found no association between elevated thyroid stimulating hormone and severe mood dysregulation in youths [3]. This contradicts the conclusion from another study published only two years earlier [4].

This is by no means intended to be an exhaustive review of the subject, but it tends to highlight the unsettle nature of the research conclusions reached thus far.

1. Amos, J. J., M.D., and J. Chahal, M.D. (2010). Management of psychiatric syndromes due to endocrine and metabolic diseases. Psychosomatic Medicine: An Introduction to Consultation-Liaison Psychiatry. J. J. Amos, M.D., and R. G. Robinson, M.D. New York, Cambridge University Press: 184-192.

2. de Jongh, R. T., P. Lips, et al. (2011). “Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals.” European Journal of Endocrinology 165(4): 545-554.
Objective To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate.Design A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam.Methods TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal)Results Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22–0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59–1.35 and 0.69, 95% CI 0.40–1.20 respectively).Conclusions This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population.

3. Zepf, F. D., T. D. Vloet, et al. (2011). “No association between affective and behavioral dysregulation and parameters of thyroid function in youths.” Journal of Affective Disorders 134(1-3): 478-482.
Objective Evidence from adults suggests that changes in thyroid function are associated with the development of bipolar disorder (BD) and severe mood dysregulation. A dysregulation profile based on the Child Behavior Checklist (CBCL-DP) describes a phenotype with severe mood problems in youth. The present study investigated whether altered thyroid functioning in youths is associated with the severe mood dysregulation symptoms characterized by the CBCL-DP. Methods We analyzed the thyroid function data from 262 children and adolescents (n=262 for serum TSH, n=148 for free triiodothyronine [fT3] and n=153 for free thyroxine [fT4]) with their CBCL-DP composite score. We created and compared high CBCL-DP and low CBCL-DP subgroups with regard to their serum TSH, fT3 and fT4 concentrations as well as the presence or absence of subclinical hypothyroidism. Results We did not detect between-group differences in serum TSH, fT3 and fT4 concentrations, nor were there significant correlations between youths’ CBCL-DP scores and their serum TSH, fT3 and fT4 concentrations for either the whole sample or any subgroup. Post-hoc power analyses indicated that adequate to moderate power existed to detect between-group differences in fT3 and fT4 concentrations, respectively, but that larger TSH samples would be required to detect the same differences in those concentrations. Limitations This study had a retrospective design, fewer females than males, and reduced power with respect to TSH concentrations. Conclusions The present investigation does not support the association between elevated serum-TSH concentrations and severe mood dysregulation in youths. However, these findings should be confirmed in future large-scale studies.

4. Holtmann, M., E. Duketis, et al. (2010). “Severe affective and behavioral dysregulation in youth is associated with increased serum TSH.” Journal of Affective Disorders 121(1-2): 184-188.
Background The relationship of bipolar disorder (BD) and altered thyroid function is increasingly recognized. Recently, a behavioral phenotype of co-occurring deviance on the Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AB) syndrome scales has been identified as the Child Behavior Checklist Dysregulation Profile (CBCL-DP), which itself has been linked to BD. This study tested for differences in thyroid function within a sample of n=114 psychiatric children and adolescents with and without the CBCL-DP. Method A CBCL-DP score was generated based on the composite of the crucial CBCL syndrome scales (A/D, AP, AB). Participants with a CBCL-DP score ≥ or =2.5 SDs above average constituted the CBCL-DP subgroup (n=53). Those with CBCL-DP scores of 1 SD or less above average percentile were regarded as controls (n=61). Groups were compared regarding serum levels of TSH, fT3 and fT4. Results In participants showing the CBCL-DP, basal serum TSH was elevated compared to controls. More CBCL-DP subjects than controls showed subclinical hypothyroidism. No differences were observed for serum fT3 and fT4 levels. Conclusions This is the first study to demonstrate associations between CBCL-DP and subclinical hypothyroidism. Future research should address the long-term outcome of CBCL-DP with coexisting hypothyroidism, the potential benefits of supplementation with thyroid hormone, and the association between severe dysregulation and the bipolar spectrum.

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