Case 2 concluded Three months later, repeat testing reveals a negative thyroid antibody test, a TSH elevated to 9 mU/L, and a free T4 and fasting lipid profile within normal limits. S.J. and his physician discuss the pros and cons of thyroid replacement and decide to retest his thyroid function in 6 months with a repeat TSH.
Comment Should individuals with subclinical disorders be treated? How frequently should their thyroid function tests be monitored? The answers vary greatly among clinicians.
Some experts argue that treatment improves behavioral function and decreases lipid levels. Some clinicians take a “wait and see” approach because values can normalize in approximately 10% of patients.6,8 Others treat based on presence of symptoms and risk of progression to overt thyroid failure (Table 2). If treatment is elected, only partial supplementation is usually needed. Most clinicians will start with a dose of 25 ug/d of T4 with adjustment every 6 to 8 weeks until the TSH is normalized.
Unless subclinical hyperthyroidism is secondary to over-replacement with exogenous thyroid hormone, this condtion can be more difficult to treat than subclinical hypothyroidism. Antithyroid therapy should be discussed with patients who have symptoms suggestive of hyperthyroidism, osteoporosis, recurrent atrial fibrillation, or thyroid gland nodules. Consultation with an endocrinologist can help clarify the risks and benefits and determine the specific antithyroid treatment appropriate for each patient.
Case 3: Medications and thyroid abnormalities
R.K., 56, has a long history of bipolar disorder. Upon presenting to his psychiatrist for routine follow-up, he reports a lack of energy but denies other symptoms of mania or depression. He periodically leaves work early or takes a short nap in his office to combat the fatigue. He feels that this may simply be part of “getting old.” He denies any new medical problems and has seen his family physician in the last year. He states that he has been compliant with his medications, lithium and olanzapine. He appears slightly withdrawn and blunted but otherwise there are no abnormal features.
His lithium level, thyroid function, or kidney function had not been checked for 7 months. Subsequent testing reveals an elevated TSH (50 mU/L), a normal kidney profile, and a lithium level in the therapeutic range.
Challenge In psychiatric settings, lithium carbonate is the drug most commonly associated with decreased thyroid function. Lithium interferes with both thyroid hormone synthesis and secretion. One-half of those taking lithium chronically develop goiter, and 40% develop subclinical or overt hypothyroidism.9-11
Many patients treated with lithium test positive for antithyroid antibodies. It is unclear if this finding represents a chronic autoimmune thyroiditis or is secondary to lithium treatment itself. In any case, patients taking lithium face an increased risk of thyroid failure. Other risk factors for thyroid failure include female gender and duration of treatment. Lithium dosage does not seem to be related to risk.
Clinicians differ on the frequency of thyroid monitoring for patients taking lithium. For patients without a history of thyroid dysfunction, annual TSH testing is likely sufficient.
Other medications affecting thyroid hormone production include methimazole, propylthiouracil, and iodide-containing drugs and dyes. Methimazole and propylthiouracil are given to patients intentionally with overt hyperthyroidism and interfere with hormone synthesis. Patients receiving medications or dyes containing iodide may also be susceptible to hypothyroidism. These agents are partially deiodinated after they are given and therefore can cause transient or prolonged decreases in thyroid production.
EUTHYROID SICK SYNDROME
In consultative work, psychiatrists often confront abnormal thyroid tests in critically ill patients. Euthyroid sick syndrome can be a challenge to distinguish from ill patients with true thyroid or pituitary dysfunction. This syndrome is common in hospitalized patients and has been documented in more than 50% of patients in some settings.14
Abnormal thyroid tests are observed in a variety of medical conditions including heart failure, myocardial infarction, renal failure, liver disease, infections, stress, trauma, starvation, and autoimmune disorders. There is considerable debate about the meaning of these test abnormalities, and to date no conclusive intervention to correct abnormalities has proven to be consistently effective in ill patients.
The complex results of testing contribute to the confusion. An isolated low T3 is the most common lab abnormality found in nonthyroidal illness, related to a decrease in T4 enzymatic conversion to T3. Many disease states decrease this enzyme’s (5’-deiodinase) activity. Unlike T3, TSH and T4 levels stay within normal limits in mild to moderately ill patients.
In patients who are moderately ill or who have been ill for a longer time, T4 levels fall with T3. In more severe and critically ill patients, the TSH level can decrease as well.
T4 can be elevated in sick patients without thyroid dysfunction. With this pattern, the TSH and T3 levels are normal or high. The clinical meaning of these abnormalities is unclear. Some studies suggest that the degree of thyroid hormone suppression correlates with disease severity and prognosis. Both decreased T3 and T4 levels have been shown to correlate with mortality in some disease states.15 Debate remains as to whether these findings represent a maladaptive process or a protective response to illness.
III patients with hyperthyroidism generally have an elevated serum free T4 and T3 with an undetectable TSH. Ill patients with true hypothyroidism will have a TSH greater than 20 to 30 mU/ml with suppressed T4 and T3 levels. Diagnosis is more difficult when TSH levels are mildly abnormal or when the clinician is trying to distinguish secondary hypothyroidism from the low T3, T4, and TSH pattern found in many critically ill patients. Secondary testing or clinical findings such as an enlarged gland, the presence of thyroid antibodies, or abnormalities in other pituitary hormones may point to an underlying thyroid or pituitary problem in ill patients.