Hypothyroidism—even when occult or subclinical—can cause subtle or frank changes in energy, mood, anxiety level, or cognition. Some patients’ affective symptoms remit with thyroid hormone replacement or with antidepressants only after a euthyroid state is established.

To help you recognize hypothyroidism in patients presenting with psychiatric illnesses and provide effective treatment, this article describes:

hypothyroidism’s signs and symptoms

primary and subclinical hypothyroidism, thyroiditis, central hypothyroidism, and thyroid hormone resistance

laboratory screening for thyroid dysfunction in patients with psychiatric symptoms.

Overlapping clinical signs



Thyroid hormone is required for the metabolic activity of every cell in the body. When patients experience symptoms related to abnormal functioning of the hypothalamic-pituitary-thyroid axis (Figure), psychiatrists often are the first professionals they consult.

Diagnosis of thyroid disorders is based on biochemical and clinical data (Box 1),1 which might not be congruent. Clinical symptoms of hypothyroidism, for example, are notoriously variable. Severe biochemical hypothyroidism may be associated with mild clinical symptoms, whereas mild biochemical hypothyroidism may be associated with severe symptoms.2

Patients with thyroid disturbance and psychiatric symptoms most often are diagnosed with a depressive-spectrum syndrome. Most common are:

atypical depression (which may present as dysthymia)

bipolar spectrum syndrome (including manic-depression, mixed mania, bipolar depression, rapid-cycling bipolar disorder, cyclothymia, and premenstrual syndromes)

borderline personality disorder

or psychotic disorder (typically paranoid psychosis).

Psychiatric symptoms of hypothyroidism (Table 1) are often prominent or even primary. Patients commonly show:

impaired attention, concentration, learning, and memory

psychomotor slowing

and/or mental dullness.

Table 1

Hypothyroidism’s psychiatric signs and symptoms

Cognitive changes Impaired memory, psychomotor slowing, reduced attention span Vegetative symptoms Hypersomnia, sleep apnea, fatigue, lethargy, apathy, anergia, low libido Mood changes Depression, mood instability, mania, anxiety Other Psychosis

Box 1

Thyroid dysfunction: Psychiatric patients show increased risk Psychiatric patients—particularly those with mood disorders—are more likely to exhibit biochemical evidence of frank or subclinical hypothyroidism, hyperthyroidism, and autoimmune thyroiditis than the general population. In a study of 17,533 Americans,1 approximately 12% had thyroid abnormalities and 80% of these were hypothyroid. An additional 17% of women and 9% of men tested positive for antithyroid antibodies. Biochemical hypothyroidism was defined as TSH >4.5 mIU/L, with low total T4, and subclinical hypothyroidism as TSH >4.5 mIU/L with normal T4 levels. Population studies and other data have led some endocrinologists to regard serum TSH levels >2.5 mIU/L as abnormally high.

Figure Thyroid hormone regulation: The hypothalamic-pituitary-thyroid axis







Thyroid-stimulating hormone (TSH, thyrotropin) released into circulation by the pituitary stimulates the thyroid to synthesize and release thyroid hormone, including triiodothyronine (T3) and thyroxine (T4). TSH is regulated by hypothalamic elaboration of thyrotropin-releasing hormone (TRH), which stimulates TSH release in a dose-dependent manner. Negative feedback from T3 and T4 downregulates TRH gene expression and restrains the pituitary from responding to TSH. Most T3—the active hormone—is formed in circulation or in target tissues by deiodination of T4 by selenium-containing enzymes.

Illustration for Current Psychiatry by Rich LaroccoThe degree of impairment may depend on the patient’s normal functional level. For example, a well-educated patient of mine with thyroiditis-related hypothyroidism reported word-finding difficulties. Instead of asking her husband to take a bottle of wine from the rack, she asked him to take a bottle of wine from the “thing.”

Loss of vitality, fatigue, lethargy, hypersomnia (especially if sleep apnea is present), and depressed mood also are commonly seen.

Depressive symptoms. Hypothyroid patients usually meet several criteria for a major depressive episode—such as concentration difficulties, lassitude, low libido, and sometimes pessimism or sadness—and symptoms improve after sustained thyroid hormone replacement therapy.3 Women with mild hypothyroidism who screen negative for a psychiatric syndrome show statistically significant mood improvement and improved verbal fluency after 6 months of levothyroxine replacement therapy.4

In some patients with no clear evidence of a biochemical or clinical thyroid disorder, mood symptoms nevertheless respond to thyroid hormone augmentation of antidepressants.5

Anxiety symptoms. Occasionally thyroid dysfunction is seen in patients with anxiety disorders, including panic disorder, agoraphobia, social phobia, performance anxiety, post-traumatic stress disorder, and generalized anxiety disorder.6

It may seem counterintuitive, but hypothyroidism is probably as common as hyperthyroidism in extremely anxious patients. Both hypoand hyperthyroidism are seen much more often in patients with panic-level anxiety than in the general population.

In a sample of 144 consecutive female psychiatric patients with a lifetime history of panic disorder and/or agoraphobia:

27% had a history of thyroid disorder

17% had hypothyroidism

8% had hyperthyroidism.7

Hypothyroid symptoms. Associated symptoms of hypothyroidism (Table 2) may include cold intolerance, lack of or reduced perspiration, dry skin, constipation, lethargy, psychomotor slowness, and subjective paresthesias and muscle pains. Edema is often present. The face typically is swollen or “puffy” in the morning, but by evening the lower legs (and not the face) are edematous.