Thyroid dysfunction is known to cause a variety of neuropsychiatric symptoms, including mood disorders, psychosis, and cognitive dysfunction. However, the mechanism by which thyroid hormone causes psychiatric disturbance is not fully understood. In the brain, the active form of thyroid hormone, T3, binds to nuclear receptors, which are widely distributed, and alters gene transcription. Thyroid receptors located in the limbic system are theorized to cause the psychiatric manifestations of hypothyroidism.7
Affective disorders. Depressed mood is a well-known and accepted symptom of hypothyroidism. Clinical symptoms such as poor concentration, weight changes, memory issues, and poor energy are common overlapping symptoms of depression and hypothyroidism, so routine screening in depressed patients is prudent. In fact, approximately 40% of patients with clinical hypothyroidism have significant depressive symptoms.8
The connection between subclinical hypothyroidism and depressed mood is more controversial. Some studies have found higher frequency and severity of depression in patients who have subclinical hypothyroidism than in euthyroid individuals.9 There is also evidence that subclinical hypothyroidism can negatively affect the treatment of depression by interfering with antidepressant response.10
Hypothyroidism can also present with mania. While mania is an uncommon presentation for hypothyroidism, several cases have been described.11,12 In these cases, the mania has resolved with thyroid replacement. There are also case reports of aggressive titration of levothyroxine causing secondary mania.13
There appears to be a relationship between bipolar disease and hypothyroidism. Antithyroid peroxidase antibodies have been found at higher rates in patients who have bipolar disorder than in the general public.14 Treatment of hypothyroidism in patients with rapid cycling bipolar disorder has been found to decrease the severity and frequency of manic episodes.15
Psychosis. Classic myxedema madness was first described by Asher16 in 1949 in a case series of patients with severe hypothyroidism and psychosis. While myxedema madness most typically presents as delirium, psychotic symptoms secondary to hypothyroidism may present in a patient who does not have altered consciousness or cognitive impairment. In fact, an array of psychotic symptoms, including delusions, visual and auditory hallucinations, paranoia, and thought disorders, have been reported secondary to hypothyroidism.17
Psychosis does not necessarily appear to be related to the severity of the thyroid dysfunction because psychosis has been reported in both clinical and subclinical hypothyroidism.18 While psychosis can be the presenting symptom that brings a patient to clinical attention, it typically occurs late in the disease course.
Cognitive dysfunction. Cognitive impairment is common in hypothyroidism and can range from mild to severe. Deficits vary from impaired concentration and slowed processing speed to general declines in intelligence, psychomotor speed, visual-spatial skills, and memory. Cognitive deficits associated with hypothyroidism tend to be more pronounced in the elderly. In fact, hypothyroidism is thought to be one of the reversible causes of dementia, and therefore a screening TSH test is indicated in all dementia workups. However, severe hypothyroidism that has progressed to dementia is not always fully reversible, even after appropriate treatment.
If thyroid dysfunction is suspected clinically, the preferred initial test is serum TSH. If the serum TSH level is abnormal, the TSH should be rechecked along with a free T4 level. The results of these laboratory tests will allow the classification of the patient’s thyroid condition (Table 3). Primary hypothyroidism is diagnosed when the TSH level is elevated and the free T4 level is low. Subclinical hypothyroidism is the diagnosis when the TSH level remains high on repeated testing and the free T4 level is found to be in the normal range. A low serum free T4 level combined with a low, or inappropriately normal, TSH level likely represents second-ary hypothyroidism.
Dr Estabrook is a Psychosomatic Medicine Fellow in the department of psychiatry and behavioral medicine, and Dr Heinrich is Associate Professor in the department of psychiatry and behavioral medicine and the department of family and community medicine at the Medical College of Wisconsin in Milwaukee. The authors report no conflicts of interest concerning the subject matter of this article.
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