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Medicine in Brief, Cases that Test Your Skills

Subclinical hypothyroidism: Merely monitor or time to treat?

Vol. 8, No. 2 / February 2009

Principal Source: Roberts LM, Pattison H, Roalfe A, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006;145:573-581.—Discussant: Y Pritham Raj, MD

Practice Points

  • Subclinical thyroid dysfunction is largely a laboratory diagnosis that merits observation but not necessarily treatment.
  • Watchful waiting is preferable in patients age ≥65 with mild subclinical hypothyroidism (TSH <10 mU/L) unless they have prominent mood, cognitive, or medical conditions—such as congestive heart failure or hyperlipidemia—that could benefit from early thyroid replacement.
  • In adults age <65, consider TSH 4.5 to 10 mU/L as a threshold for initiating thyroid replacement, particularly if anti-TPO antibodies are present (although prevailing recommendations still favor the watchful waiting approach).6

Thyroid dysfunction enters the differential diagnosis for most mood, anxiety, thought, and cognitive disorders. Because more than one-half of the estimated 27 million Americans with hyperthyroidism or hypothyroidism are undiagnosed,1 the American Thyroid Association recommends universal screening for thyroid dysfunction after age 35, with a recheck every 5 years. Although some clinicians feel this recommendation is excessive, strategic screening with a thyroid-stimulating hormone (TSH) test is important for patients with psychiatric illnesses.

If a patient’s TSH is abnormal, repeating the test while measuring the free thyroxine (T4) and in most cases the antithyroid peroxidase antibody (anti-TPO) has good clinical value. Anti-TPO antibodies are a useful biomarker for autoimmune thyroid disease, such as Hashimoto’s thyroiditis or Graves’ disease. If laboratory findings suggest the hypothyroid spectrum, a fasting lipid profile may help determine risk of adverse cardiovascular outcomes.


Symptoms of hypothyroidism—indicated by an elevated TSH (usually >20 mU/L) and low T4—overlap with psychiatric illness (Table) but are easy to treat. Psychiatrists who are accustomed to calculating weight-based dosing of medications such as lithium and valproic acid may have little difficulty initiating levothyroxine replacement (typically 1.6 mcg/kg/day) for patients with overt hypothyroidism. Treating hyperthyroidism (low TSH and high T4) can be more complex and generally is left to an internist or endocrinologist. But how should you treat subclinical thyroid dysfunction?


Hypothyroidism symptoms that indicate treatment

With psychiatric overlap



Cognitive impairment (forgetfulness)

Difficulty concentrating/learning

Weight gain/fluid retention

Somatic symptoms

Dry, itchy skin

Brittle nails and hair



Heavy and/or irregular menses

Increased miscarriage risk

Cold sensitivity

Treat or wait?

Subclinical hypothyroidism (SH)—in which T4 is normal—usually is a laboratory diagnosis defined in a spectrum:

  • TSH of 4.5 to 10 mU/L is mild SH (80% of cases)
  • TSH of 10 to 20 mU/L is more severe SH.

SH is a well-established risk factor for depression. One study found a nearly 3-fold higher lifetime prevalence of depression in young and middle-aged women with SH.2 To the practicing psychiatrist, these results may sound like a mandate to treat all patients with SH—particularly those with depression. Consider, however, that in a prospective observational study the TSH of >37% of patients with SH returned to normal with observation alone.3 In fact, <27% of patients with SH went on to develop overt hypothyroidism during the study period, on average within 31.7 months.

A second study that would argue against treating patients with mild SH noted decreased cardiovascular and noncardio-vascular mortality among elderly patients with elevated TSH,4 implying that SH may be protective compared with the euthyroid state, at least among octogenarians.

Still, do mood, anxiety, or cognitive symptoms in SH patients merit earlier, more aggressive treatment? This question was addressed by a recent cross-sectional study that demonstrated no correlation between mood and SH.5 Although statistically significant associations were seen among anxiety, cognition, and elevated TSH, the magnitude of the associations lacked clinical relevance. This study was designed to further assess an earlier inconclusive review.6

Ultimately, treating SH—although easy to do—may have little impact on your patient’s overall mood and cognition until TSH is ≥10 mU/L.

Drug brand names

  • Levothyroxine • Levoxyl, Synthroid
  • Lithium • various
  • Valproic acid • Depakene


Dr. Raj is a consultant to Alpharma and a speaker for AstraZeneca.


1. American Association of Clinical Endocrinologists. Thyroid fact sheet. Available at: Accessed January 14, 2009.

2. Haggerty JJ, Stern RA, Mason GA, et al. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry. 1993;150:508-510.

3. Diez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab. 2004;89(10):4890-4897.

4. Gussekloo J, van Exel E, de Craen AJM, et al. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292:2591-2599.

5. Roberts LM, Pattison H, Roalfe A, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006;145:573-581.

6. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-238.

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