Discuss this article at www.facebook.com/CurrentPsychiatry
Many endocrine disorders can manifest as depression, including relatively rare disorders such as Cushing’s syndrome (hypercortisolism) or Conn’s syndrome (primary hyperaldosteronism) as well as common ones such as diabetes mellitus. Most clinicians do not routinely screen for adrenal disorders when evaluating depressed patients because the yield is low, but do screen for thyroid disease because these disorders often mimic depression. The following 3 cases from my practice illustrate some nuances of screening and treating depressed patients with suspected thyroid abnormalities.
CASE 1: Feeling ‘like an 80-year-old’
Ms. A, age 25, has a gastrointestinal stromal tumor (GIST) and states that she feels “like an 80-year-old woman.” She is sore all over with facial swelling, abdominal cramping, and fatigue. This feeling has worsened since she started chemotherapy with sunitinib for the GIST. Her Patient Health Questionnaire-9 (PHQ-9) score is 14 out of 27, indicating moderate depression. As part of a workup for her depression, what general laboratory tests would be most helpful?
Because Ms. A is of menstruating age, check hemoglobin/hematocrit levels to evaluate for anemia. Monitoring electrolytes would allow you to assess for hypernatremia/hyponatremia, hyperkalemia/hypokalemia, and impaired renal function, all of which could cause depressive symptoms. Depending on Ms. A’s habitus or risk of metabolic syndrome, a fasting blood glucose or hemoglobin A1C test to screen for diabetes mellitus might be valuable because depression may be associated with diabetes.1 A1C is a preferred primary screening test for diabetes (≥6.5% constitutes a positive screen) based on revised clinical practice recommendations of the American Diabetes Association. A1C is available as an office-based test that requires just a drop of blood from a finger prick and does not require a fasting blood sample or a full laboratory analysis.
A popular test for a workup of depression is serum 25-hydroxyvitamin D [25(OH)D] (vitamin D), particularly for patients who live in areas with limited exposure to ultraviolet B radiation from sunlight.2 In a study of older adults, vitamin D levels were 14% lower in patients with minor depression and 14% lower in patients with major depressive disorder compared with controls. This study suggests that depression severity is associated with decreased serum vitamin D levels,3 but the association between depression and vitamin D insufficiency and deficiency is unknown. Checking sex hormones also may be helpful depending on the patient’s symptoms, because testosterone deficiency in men and dehydroepiandrosterone deficiency in women can have a direct impact on a patient’s libido and overall sense of well-being. If repleted, improved levels of sex hormones can lead to a dramatic improvement in mood as well.
Because more than one-half of the estimated 27 million Americans with hyperthyroidism or hypothyroidism are undiagnosed, the American Thyroid Association recommends universal screening for thyroid dysfunction after age 35, with a recheck every 5 years.4 However, checking serum thyroid-stimulating hormone (TSH) levels this often may not be cost-effective. Typically, I do not follow this recommendation when assessing or treating asymptomatic individuals, but Ms. A has symptoms of hypothyroidism (Table 1) and is taking a medication—sunitinib—thought to be associated with hypothyroidism.5 Her serum TSH was very high (110 mIU/L; range 0.28 to 5.00) and her serum free T4 (FT4) was low (0.5 ng/dL; range 0.7 to 1.8). These values were consistent with overt hypothyroidism, defined as low FT4 and elevated TSH levels. This is in contrast to subclinical hypothyroidism (SH), which is defined as having an elevated serum TSH with normal thyroid hormone (T3 and T4) levels. SH presents in 5% of young patients (age <45) and increasingly is being diagnoses in older patients (age >55), who are most likely to suffer adverse effects in mood or cognition.6
Table 1
Hypothyroidism symptoms
| Psychiatric overlap |
| Fatigue |
| Hypersomnolence |
| Cognitive impairment (forgetfulness) |
| Difficulty concentrating or learning |
| Weight gain or fluid retention |
| Somatic signs and symptoms |
| Dry, itchy skin |
| Brittle hair and nails |
| Constipation |
| Myalgias |
| Heavy and/or irregular menstrual cycle |
| Increased rate of miscarriage |
| Sensitivity to cold |
CASE 1 CONTINUED: A classic case
Ms. A is started on a full levothyroxine replacement dose of 1.6 μg/kg/d. For hypothyroid patients who do not have cardiac symptoms, weight-based replacement is thought to be safe and more convenient than starting with a low dose and titrating up.7 Ms. A responds quickly. At 6-week follow-up—the recommended time interval for repeat thyroid lab testing after initiating thyroid replacement—her depressive symptoms are markedly improved and her PHQ-9 score is 6, indicating mild depression.
CASE 2: Chronic pain, low mood, and fatigue
Ms. B, age 62, has fibromyalgia and chronic back pain. She takes cyclobenzaprine, 5 mg 2 to 3 times daily, and oxycodone, 40 mg/d, and describes mild depressive symptoms when she presents for routine follow-up. Most of her complaints are related to chronic pain, but she has a history of low mood and fatigue. She says she was prescribed levothyroxine, but is unable to remember if she stopped taking it because of financial constraints or laboratory/clinical improvement. Her neurologist recently checked her serum TSH, which was elevated at 8.1 mIU/L. Is it best to restart thyroid replacement or wait 6 weeks and recheck her thyroid panel?