Psychiatrists commonly order thyroid testing and are often the first to confront abnormal thyroid test results. As thyroid testing has become more sophisticated and sensitive (Box 1), the interpretation and management of abnormal or slightly abnormal results has become increasingly complex. What’s more, older individuals, hospitalized patients, and those with psychiatric illness often present with subtle laboratory abnormalities.
Hyperthyroidism and hypothyroidism are highly prevalent disorders, especially in women and the elderly. Thyroid dysfunction is the second most common endocrine disorder after diabetes among elders. In the three cases that follow, some of the problems and solutions in dealing with thyroid testing are presented.
Case 1: Depression and thyroid abnormalities
J.R., 67, has a history of hypertension. She was referred for evaluation of depressive symptoms. She reports 3 months of increasing fatigue, lethargy, and poor motivation. Her weight has increased by 10 pounds over this period. Her physical exam, ECG, and chest x-ray are normal. She is well groomed and slightly overweight. Her medications have not changed recently and include hydrochlorothiazide 25 mg/d and an aspirin a day.
J.R. reports no history of treatment for psychiatric illness, denies current use of alcohol, tobacco, or illicit drugs, exhibits no abnormal movements or psychomotor changes, and her speech is articulate. Her mood is depressed, and her affect is restricted. She is not suicidal or homicidal, and her exam reveals no psychotic features.
Challenge Patients with thyroid abnormalities often present with psychiatric complaints. Classically, hypothyroidism can present like a depressive episode with similar symptoms of fatigue, anhedonia, weight gain, and sleep disturbance. Patients with hypothyroidism, however, may have physical complaints as well, which should alert the clinician to an underlying thyroid disorder. Typical physical complaints include hair loss, weight gain, dry skin, cold intolerance, constipation, muscle cramps, and joint pains. Women may also complain of menstrual disturbances such as menorrhagia, and may have trouble with fertility.
SCREENING FOR HYPOTHYROIDISM AND HYPERTHYROIDISM
An elevated or decreased TSH suggests thyroid dysfunction and should always be evaluated.
A low free T4 confirms the diagnosis of hypothyroidism. A low total T3 or free T3 is not always present but is associated with severe forms of hypothyroidism. The hallmark of hyperthyroidism is an elevated free T4 level or free T3 level or both. In a primary thyroid disorder, the TSH is below 0.1 U/L or undetectable.
Here is a description of these tests and what they mean:
- TSH (thyroid-stimulating hormone) is a pituitary hormone that acts on the thyroid gland to increase thyroid hormone secretion. Measurement of TSH is the most sensitive test to screen for hypothyroidism and hyperthyroidism as long as a second-generation assay is used (0.05 mIU/L). Thyroid testing should always begin just with the TSH test. Ordering a free T4 test at the same time is redundant and costly.
- T4 (thyroxine) is best and most accurately measured in its unbound free form. Of all the tests that measure thyroxine, free T4 most accurately reflects unbound thyroid hormone, which is physiologically active. Also, several variables (e.g. pregnancy, disease states, medications) alter total T4 levels by increasing or decreasing thyroid binding hormones. A free T4 test should always follow an abnormal TSH.
- T3 (triiodothyronine) is produced in the thyroid and in peripheral tissues via the enzymatic conversion of T4. Like T4, it is bound and unbound in the serum by thyroid binding globulin, and either form can be measured. T3 should be measured when the TSH is abnormal but the free T4 is within normal limits.
- T3 resin uptake is used to calculate indirectly free T4 and should only be ordered if a free T4 test is unavailable.
- Thyroid antibody tests can help uncover the underlying cause of thyroid dysfunction. These tests lack sensitivity and specificity and should not be used to rule out cancer. Thyroid peroxidase antibodies (antithyroglobulin) and antimicrosomal antibodies are associated with Hashimoto’s thyroiditis and Graves’ disease. Thyroid-stimulating immunoglobulin (TSI) or thyroid-stimulating hormone receptor antibodies are almost always unique to Graves’ disease.
- A radioactive iodine uptake thyroid scan (RAIU) is the best test to determine the cause of hyperthyroidism. Uptake is elevated in most common conditions causing hyperthyroidism, but the pattern of uptake differs. In the context of hyperthyroidism, absent uptake should raise a red flag for nonfunctioning nodules that can be either benign or malignant. A thyroid scan is unhelpful and should not be ordered in working up hypothyroidism.
- Thyroid ultrasound can characterize gland size and nodularity but cannot distinguish benign from malignant masses.
- Fine-needle aspiration biopsy (FNAB) is the best test to distinguish benign and malignant nodules.
What makes the diagnosis difficult and often missed is that some patients have hypothyroidism with minimal or no symptoms. This is especially true in elders because many of the signs and symptoms of hypothyroidism are attributed to “normal” aging. In one recent review of women older than 70 who were screened in an office-based setting, 2% were diagnosed with unsuspected overt hypothyroidism.1 Because classical exam and laboratory findings associated with hypothyroidism tend to present later in the disorder, many patients with thyroid dysfunction have “normal” exams.