Evidence-Based Reviews

Identifying hypothyroidism’s psychiatric presentations

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Thyroid hormone resistance ranges from euthyroid and clinically transparent to profoundly hypothyroid, and different organs in the same patient may show different sensitivities to thyroid hormone. Clinical features vary, depending on the strength of thyroid hormone resistance.

Early emergence of resistance (as would be expected in someone with an inherited thyroid hormone receptor abnormality) leads to developmental problems, including:

  • short stature
  • mental or learning disabilities (including attention deficits).

In a study of 18 families with strong history of generalized resistance to thyroid hormone, 70% of affected children met diagnostic criteria for attention-deficit/hyperactivity disorder.12

Box 2

When to try thyroid hormone therapy for psychiatric symptoms

Target psychiatric symptoms for prescribing replacement thyroid hormone are depression; mood cycling or instability; low energy, fatigue, or lethargy; cognitive impairment (Table 1); and psychosis, if present. Because these symptoms are not specific to thyroid dysfunction, institute thyroid hormone only when biochemical evidence of compromised or suboptimal thyroid function is also present.

Exceptions to this rule may include patients with target psychiatric symptoms and:

  • other hypothyroidism symptoms (Table 2)
  • circulating T3, free T3, or free T4 levels near the low margin of the normal range and/or TSH >3.5 to 4.0 mIU/mL.1
  • a history of inadequate response to psychopharmacologic interventions
  • symptoms of and a strong family history of thyroid disease.

Box 3

Long-term lithium therapy linked with hypothyroidism risk

Patients taking lithium for mood stabilization will likely need supplemental thyroid hormone eventually because lithium is thyrotoxic. Also, patients with bipolar mood symptoms often have coexisting thyroid abnormalities, and giving supraphysiologic thyroid hormone dosages sometimes converts those who do not respond to mood stabilizers into responders.

Thyrotropin concentrations increase within 1 day after patients start taking lithium carbonate, but without commensurate increases in T3 or T4. More often, T3 and T4 concentrations decrease in the presence of lithium. Among 150 patients maintained on lithium for 10 years, hypothyroidism, autoimmune thyroiditis, or goiter developed at rates of 1.7%, 1.4%, and 2.1% per year, respectively. The study authors suggested that long-term lithium may increase the risk for hypothyroidism in women and in patients with thyroid autoimmunity.9

Laboratory screening

TSH and thyroid hormones. The basic thyroid screen is a combination of serum levels of TSH (“sensitive TSH”) and free thyroid hormones.

TSH has a circadian rhythm, with a nocturnal surge amounting to a 50% to 200% increase over daytime levels, beginning at around 6 to 8 PM. Peak TSH pulsatile activity and levels are seen after sleep begins—usually after midnight—with trough levels and fewest TSH pulses in late morning and early afternoon.13,14 This rhythm implies that the most accurate TSH measurement may be obtained by drawing blood in the morning before 9 AM. I have seen subclinical hypothyroidism missed when clinicians relied on afternoon TSH levels.

In general medicine, TSH alone frequently is used as a routine screening tool. In psychiatric practice, however, I recommend supplementing TSH with free T3 and free T4 because thyroid system dysfunction is frequent in psychiatric syndromes. If laboratory costs are a concern, free T4 with TSH usually suffices for initial screening.

Although the unbound, free fractions of T3 and T4 are of primary interest, total T4 and total T3 are necessary to assess the thyroid gland’s synthetic capacity. When clinical evidence suggests abnormal thyroid hormone function, order repeated or serial biochemical testing. Marginal biochemical results also mandate repeat thyroid function studies, expanded to include:

  • total thyroid hormone concentrations (ideally T4 and T3)
  • antithyroid antibodies
  • serum cholesterol
  • prolactin.

Antithyroid antibodies. Obtain antithyroglobulin and antithyroid microsomal antibody titers if:

  • thyroid hormone indices are abnormal or marginal—in either direction
  • or the patient now has, has had, or has a family history of autoimmune-mediated symptoms, such as lupus erythematosus or rheumatoid arthritis.

Negative or low antithyroid autoantibody titers do not rule out thyroiditis as a cause of hypothyroidism, as these titers are most likely to be generated during periods of active inflammation.

Many autoantibodies react with thyroid-related elements. Most clinical laboratories can quantify antibodies directed against thyroid peroxidase—also called antimicrosomal antibodies—and thyroglobulin. The presence of these antibodies is associated with thyroid inflammation and a risk of progression to thyroid failure and hypothyroidism.

Other laboratory findings of hypothyroidism include hypercholesterolemia, mild hyperprolactinemia, and types of anemia (including iron-deficiency anemia with low ferritin levels).

Related resources

  • American Thyroid Association. www.thyroid.org.
  • Dunn JT. Guarding our nation’s thyroid health. J Clin Endocrinol Metab 2001;872:486-8.
  • Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646-55.
  • Sullivan GM, Mann JJ, Oquendo MA, et al. Low cerebrospinal fluid transthyretin levels in depression: correlations with suicidal ideation and low serotonin function. Biol Psychiatry 2006;60(5):500-6.

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