Psychiatric disorders and thyroid disease

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CHAPTER 41

Psychiatric disorders and thyroid disease

1. How well established is the relationship between thyroid disease and psychiatric symptoms?

Since the publication of the Clinical Society of London’s “Report on Myxoedema” in 1888, it has been recognized that thyroid disease may give rise to psychiatric disorders that can be corrected by reestablishment of normal thyroid hormone levels. Later, Asher reemphasized that patients with profound hypothyroidism may present with depressive psychosis. As outlined in Table 41-1, the symptoms of hypothyroidism often mimic those of depression, whereas those of hyperthyroidism include anxiety, dysphoria, emotional lability, and intellectual dysfunction, as well as mania or depression, the latter especially characteristic among elderly patients presenting with apathetic thyrotoxicosis.

TABLE 41-1.

CLINICAL FEATURES COMMON TO BOTH THYROID DISEASES AND MOOD DISORDERS

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Adapted from Hennessey JV, Jackson IMD: The interface between thyroid hormones and psychiatry. Endocrinologist 6:214–223, 1996.

2. What abnormalities of thyroid function are found in psychiatric disorders?

3. What abnormalities of the thyrotropin-releasing hormone (TRH) stimulation test may be observed in depressed patients?

4. Describe a mechanism for the blunted TSH response to TRH in affective disorders.

5. Can abnormalities in the TSH circadian rhythm be identified in depression?

6. Is autoimmune thyroid disease frequently present in the depressed patient?

7. What is the frequency of elevated T4 values in psychiatric patients?

8. What is the most consistent abnormality of the thyroid axis in hospitalized depressed patients?

9. What is the prevalence of hypothyroid dysfunction in psychiatric populations?

Thyroid function test abnormalities are common in older individuals. In otherwise normal female patients who are more than 60 years old, the prevalence of elevated TSH values and/or positive antithyroid antibodies is 10% or more. Subjecting apparently asymptomatic individuals with slight elevations of serum TSH but normal T4 and T3 levels to a battery of psychological tests has revealed significant differences from control subjects on scales measuring memory, anxiety, somatic complaints, and depression in many but not all studies reported. It is becoming increasingly recognized that depression is much more common in elderly individuals. Whether borderline hypothyroidism plays a role in these behavioral disturbances requires clinical attention. Further investigation should also be directed at studying the outcomes of intervention with levothyroxine.

Among alcoholic patients and those suffering from anorexia nervosa, suppressed T3 levels with elevations in reverse T3 and normal TSH values are consistent with the euthyroid sick syndrome. These findings likely result from caloric deprivation.

10. Which medications affect thyroid function and thyroid function tests?

11. How does lithium affect the pituitary-thyroidal axis?

12. What is the most common thyroid disorder in lithium-treated patients?

13. How does phenytoin affect laboratory tests and the function of the thyroid?

The effects of phenytoin (Dilantin), occasionally used for bipolar disorder, on thyroid function are quite complex. Suppressed values of total T4 and, occasionally, free T4 are observed in a significant minority of patients who are treated on a long-term basis with phenytoin alone and in more than 75% of patients in whom the drug is combined with carbamazepine (Tegretol). The lower total T4 levels are likely secondary to displacement of T4 from thyroxine-binding globulin (TBG), whereas the reduced free T4 levels result from enhanced clearance of T4 through phenytoin-induced hepatic microsomal oxidative enzyme activity. Generally, the suppressed T4 levels are accompanied by normal T3 and free T3 levels and normal TSH concentrations. Normal basal TSH values with diminished TSH responses to TRH have been attributed to potential phenytoin agonism at the T3 receptor. However, other studies have suggested that this may be an assay artifact because free T4 values have been found to be normal or mildly elevated in analyses using undiluted serum.

14. Describe the effects of carbamazepine on thyroid function.

15. How do phenobarbital, valproic acid, and other psychotropic medications affect thyroid function?

16. How do antidepressant therapies affect thyroid function?

Antidepressants do not generally cause abnormal peripheral thyroid hormone levels but may affect thyroid hormone metabolism in the central nervous system (CNS). Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) appear to promote activity of type 2 deiodinase (D2), which increases conversion of T4 into T3 in the brain. However, peripheral circulating total T4 and free T4 levels, often show a modest decline, though still within the normal range after treatment with various pharmacologic classes of antidepressants, or electroconvulsive therapy (ECT). There are case reports of sertraline-, paroxetine-, and escitalopram-related asymptomatic hypothyroidism, but more recent studies evaluating fluoxetine and sertraline have shown no clinically significant change in thyroid function test results.

17. Are there caveats for antidepressant use in individuals with thyroid disease?

18. Has T4 been used as sole treatment for depression?

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