Mild SH typically is defined as TSH between 4.5 and 10 mIU/L. In contrast, TSH between 10 and 20 mIU/L is considered severe SH. Because Ms. B did not have prominent new symptoms, I felt it was reasonable to wait the recommended 6 weeks before rechecking her thyroid function. At follow-up, Ms. B’s TSH was 4.64 mIU/L and her FT4 was normal: 0.7 ng/dL. Thyroid replacement was not indicated because she did not have obvious symptoms and treating SH does not impact overall mood and cognition until TSH is ≥10 mIU/L.8,9
CASE 2 CONTINUED: Prominent symptoms emerge
Ms. B returns several months later. Another clinician prescribed duloxetine, titrated from 30 mg to 60 mg, for worsening fibromyalgia. Her depressive symptoms are more prominent at this visit, and her PHQ-9 score has risen from 7 to 14, indicating moderate depression. She says previously she failed or poorly tolerated several antidepressants—fluoxetine, sertraline, and citalopram—but was hoping for a pharmacologic adjustment. Most evidence-based augmentation algorithms for treating major depression start with adding a second “traditional” antidepressant such as bupropion, then move to lithium, second-generation antipsychotics, or lamotrigine.10 But what about thyroid hormone augmentation?
Thyroid hormone often is on the lower rungs of depression treatment algorithms despite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial data. The data suggest triiodothyronine’s (T3) lower side effect burden and ease of use may offer an advantage over lithium augmentation for depressed patients who have failed several medication trials.11 Liothyronine sodium (triiodothyronine) is a relatively benign medication with potential for augmentation when started at 25 to 50 mcg/d concurrently with antidepressants such as sertraline.12 Unfortunately, most augmentation trials with T3 have been short-term—generally 4 to 8 weeks. In my practice, T3 has limited application; I use it mainly for patients with treatment-resistant depression who have failed several other treatments.
Lithium, the comparison medication to thyroid hormone in the third augmentation arm of the STAR*D trial, requires an annual check of thyroid function (TSH testing) to properly monitor for potential lithium-related hypothyroidism or thyroiditis. Hypothyroidism, for which thyroid replacement is required, with lithium therapy is common, affecting 8% to 27% of patients.13 Patients who rapidly gain weight at the beginning of lithium treatment seem to have a higher risk of developing hypothyroidism.13 However, the risk of developing lithium-induced hypothyroidism is tied to the length of treatment; the longer a patient has been treated with lithium, the greater the risk of developing lithium-induced hypothyroidism.
CASE 3: Unable to slow down
Mr. C, age 45, has a 20-year history of major depression controlled reasonably well with paroxetine, 40 mg. He presents with escalating anxiety, depression, and irritability. His wife is concerned about his overwhelming thoughts of death, especially because Mr. C’s father committed suicide 30 years ago under similar circumstances. Mr. C has been tremulous for the past month and has not been sleeping well. He feels like he is “in constant motion” and unable to slow down. He screens in the “highly likely” range for bipolar disorder on the Bipolar Spectrum Diagnostic Scale14 and is started on divalproex ER, 500 mg/d.
His thyroid function tests returns with a suppressed TSH of 0.03 mIU/L and an elevated FT4 of 3.26 ng/dL. Divalproex is discontinued and he is started on the beta blocker atenolol, 25 mg/d, to target his anxiety, tachycardia, and akathisia. TSH receptor antibody testing was positive, which, along with an abnormal radioactive iodine uptake scan, confirmed a diagnosis of Graves’ disease. He receives methimazole, 20 mg/d, as a temporizing measure. An endocrinologist completes a radioactive iodine (I-131) ablation procedure on Mr. C, which resolves his mood and anxiety symptoms.
Although hypothyroidism commonly is associated with depressive symptoms, hyperthyroidism also may present as depression. Most cases of overt hyperthyroidism are directly referred to an endocrinologist because when treating disorders such as Graves’ disease—the most common cause of hyperthyroidism, especially among women age 20 to 40—many nuclear medicine teams require the expert guidance of an endocrinologist before considering radioiodine ablation. Hyperthyroidism often is accompanied by psychiatric and somatic symptoms of an “overactive” nature (Table 2). However, older patients (age >65) with hyperthyroidism may develop apathetic hyperthyroidism, a subset that comprises approximately 10% to 15% of all hyperthyroidism cases in older adults.15 Rather than becoming nervous, jittery, and restless, patients with apathetic hyperthyroidism are depressed, lethargic, and weak, and may develop proximal myopathy or cardiomyopathy. It is essential to differentiate apathetic hyperthyroidism from typical hyperthyroidism because accurately diagnosing and treating apathetic hyperthyroidism will improve outcomes.15