A 27-year-old man comes to the office to follow up on bipolar disorder. The patient was hospitalized 6 months ago after disrobing on the subway, shouting at passengers, and attacking the security guards who tried to subdue him. He was diagnosed with bipolar disorder and started on a psychiatric medication regimen that proved effective. He has been stable from a psychiatric perspective since discharge, but today he has fatigue, constipation, and myalgias that have steadily worsened over the last month. His other medical problems include hypertension and hyperlipidemia for which he takes an antihypertensive and a statin. Temperature is 36.7 C (98 F), blood pressure is 129/72 mm Hg, pulse is 52/min, and respirations are 12/min. Examination is within normal limits. Which of the following is the most likely cause of this patient's symptoms?

Question

A 27-year-old man comes to the office to follow up on bipolar disorder.  The patient was hospitalized 6 months ago after disrobing on the subway, shouting at passengers, and attacking the security guards who tried to subdue him.  He was diagnosed with bipolar disorder and started on a psychiatric medication regimen that proved effective.  He has been stable from a psychiatric perspective since discharge, but today he has fatigue, constipation, and myalgias that have steadily worsened over the last month.  His other medical problems include hypertension and hyperlipidemia for which he takes an antihypertensive and a statin.  Temperature is 36.7 C (98 F), blood pressure is 129/72 mm Hg, pulse is 52/min, and respirations are 12/min.  Examination is within normal limits.  Which of the following is the most likely cause of this patient's symptoms?

Quizplus · Accepted Answer

This patient's fatigue, constipation, myalgias, and bradycardia are most consistent with lithium-induced hypothyroidism. Lithium is considered a first-line treatment for bipolar disorder; however, its use is associated with a number of side effects, including thyroid abnormalities and renal dysfunction. Approximately 25% of patients treated with lithium will develop hypothyroidism. A much smaller percentage will experience hyperthyroidism. Because of the drug's propensity to interfere with thyroid function, patients prescribed lithium should have baseline TSH levels drawn prior to starting therapy and TSH testing repeated every 6-12 months for the duration of treatment. Patients who develop hypothyroidism are generally managed symptomatically with addition of T4 (eg, levothyroxine) rather than discontinuation of lithium. (Choices A and H) Amitriptyline (a tricyclic antidepressant) is associated with constipation, drowsiness, and other anticholinergic side effects; vortioxetine (a serotonin reuptake inhibitor and 5-HT3 receptor antagonist) can cause nausea. Neither is associated with abnormal thyroid function. (Choices B and D) The calcium channel blocker amlodipine is associated with lower extremity edema and the ACE inhibitor lisinopril is associated with increased creatinine, hyperkalemia, cough, and angioedema. (Choices C and F) Aripiprazole and lurasidone are second-generation antipsychotics. Compared to olanzapine and clozapine (also second-generation antipsychotics), these agents have a lower risk of metabolic side effects (eg, weight gain, hyperglycemia). They are not associated with abnormal thyroid function. (Choice G) The HMG-CoA reductase inhibitor simvastatin can cause myalgias, but is not typically associated with constipation, fatigue, or bradycardia. Other side effects of statins include liver function test abnormalities and rhabdomyolysis. Educational objective: Approximately 25% of patients treated with lithium will develop hypothyroidism, requiring that all patients have regular TSH monitoring every 6-12 months. Lithium-induced hypothyroidism is generally treated with T4 supplementation rather than discontinuation of lithium. References: Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data. (http://www.ncbi.nlm.nih.gov/pubmed/26003379) Lithium toxicity profile: a systematic review and meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/22265699)

A 27-Year-Old Man Comes to the Office to Follow Up