Ms. A experienced an anxiety attack while driving home from work, with cardiac palpitations, tingling of the face, and fear of impending doom. Over the following 3 months she endured a “living hell,” consisting of basal anxiety, intermittent panic attacks, and agoraphobia, with exceptional difficulty even going to the grocery store.
A high-functioning career woman in her 30s, Ms. A also developed insomnia, depressed mood, and intrusive ego-dystonic thoughts. These symptoms emerged 10 years after a subtotal thyroidectomy for hyperthyroidism (Graves’ disease).
Hyperthyroidism’s association with psychiatric-spectrum symptoms is well-recognized (Box 1).1-4 Hyperthyroid patients are significantly more likely than controls to report feelings of isolation, impaired social functioning, anxiety, and mood disturbances5 and are more likely to be hospitalized with an affective disorder.6
Other individuals with subclinical or overt biochemical hyperthyroidism self-report above-average mood and lower-than-average anxiety.7
Ms. A’s is the first of three cases presented here to help you screen for and identify thyrotoxicosis (thyroid and nonthyroid causes of excessive thyroid hormone). Cases include:
- recurrent Graves’ disease with panic disorder and residual obsessive-compulsive disorder (Ms. A)
- undetected Graves’ hyperthyroidism in a bipolar-like mood syndrome with severe anxiety and cognitive decline (Ms. B)
- occult hyperthyroidism with occult anxiety (Mr. C).
These cases show that even when biochemical euthyroidism is restored, many formerly hyperthyroid patients with severe mood, anxiety, and/or cognitive symptoms continue to have significant residual symptoms that require ongoing psychiatric attention.6
Ms. A: Anxiety and thyrotoxicosis
Ms. A was greatly troubled by her intrusive ego-dystonic thoughts, which involved:
- violence to her beloved young children (for example, what would happen if someone started shooting her children with a gun)
- bizarre sexual ideations (for example, during dinner with an elderly woman she could not stop imagining her naked)
- paranoid ideations (for example, “Is my husband poisoning me?”).
She consulted a psychologist who told her that she suffered from an anxiety disorder and recommended psychotherapy, which was not helpful. She then sought endocrine consultation, and tests showed low-grade overt hyperthyroidism, with unmeasurably low thyroid stimulating hormone (TSH) concentrations and marginally elevated total and free levothyroxine (T4). Her levothyroxine replacement dosage was reduced from 100 to 50 mcg/d, then discontinued.
Without thyroid supplementation or replacement, she became biochemically euthyroid, with TSH 1.47 mIU/L and triiodothyronine (T3) and T4 in mid-normal range. Her panic anxiety resolved and her mood and sleep normalized, but the bizarre thoughts remained. The endocrinologist referred her to a psychiatrist, who diagnosed obsessive-compulsive disorder. Ms. A was effectively treated with fluvoxamine, 125 mg/d.
Discussion. Many patients with hyperthyroidism suffer from anxiety syndromes,8-10 including generalized anxiety disorder and social phobia (Table 1). “Nervousness” (including “feelings of apprehension and inability to concentrate”) is almost invariably present in the thyrotoxicosis of Graves’ disease.11
Hyperthyroidism-related anxiety syndromes are typically complicated by major depression and cognitive decline, such as in memory and attention.9 Thus, a pituitary-thyroid workup is an important step in the psychiatric evaluation of any patient with clinically significant anxiety (Box 2).3
Excess thyroid hormone’s link to psychiatric symptoms
The brain has among the highest expression of thyroid hormone receptors of any organ,1,2 and neurons are often more sensitive to thyroid abnormalities—including overt or subclinical hyperthyroidism and thyrotoxicosis, thyroiditis, and hypothyroidism3—than are other tissues.
Hyperthyroidism is often associated with anxiety, depression, mixed mood disorders, a hypomanic-like picture, emotional lability, mood swings, irritability/edginess, or cognitive deterioration with concentration problems. It also can manifest as psychosis or delirium.
Hyperthyroidism affects approximately 2.5% of the U.S. population (~7.5 million persons), according to the National Health and Nutrition Examination Survey (NHANES III). One-half of those afflicted (1.3%) do not know they are hyperthyroid, including 0.5% with overt symptoms and 0.8% with subclinical disease.
NHANES III defined hyperthyroidism as thyroid-stimulating hormone (TSH) <0.1 mIU/L with total thyroxine (T4) levels either elevated (overt hyperthyroidism) or normal (subclinical hyperthyroidism). Women are at least 5 times more likely than men to be hyperthyroid.4
CNS hypersensitivity to low-grade hyperthyroidism can manifest as an anxiety disorder before other Graves’ disease stigmata emerge. Panic disorder, for example, has been reported to precede Graves’ hyperthyroidism by 4 to 5 years in some cases,12 although how frequently this occurs is not known. Therefore, re-evaluate the thyroid status of any patient with severe anxiety who is biochemically euthyroid. Check yearly, for example, if anxiety is incompletely resolved.
Table 1
Psychiatric symptoms seen with hyperthyroidism
| Anxiety |
| Apathy (more often seen in older patients) |
| Cognitive impairment |
| Delirium |
| Depression |
| Emotional lability |
| Fatigue |
| Hypomania or mania |
| Impaired concentration |
| Insomnia |
| Irritability |
| Mood swings |
| Psychomotor agitation |
| Psychosis |
Causes of hyperthyroidism
Approximately 20 causes of thyrotoxicosis and hyperthyroxinemia have been characterized (see Related resources).11,13-15 The most common causes of hyperthyroidism are Graves’ disease, toxic multinodular goiter, and toxic thyroid adenoma. Another is thyroiditis, such as from lithium or iodine excess (such as from the cardiac drug amiodarone). A TSH-secreting pituitary adenoma is a rare cause of hyperthyroidism.16