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Key Points Impaired psychological well-being and depression or anxiety affect about 510% of hypothyroid patients on levothyroxine, despite normal TSH levels Persistent symptoms might be explained by factors unrelated to thyroid disease, unrecognized autoimmune disease, or inability of levothyroxine to restore T 3 levels in serum and all target tissues Randomized clinical trials have in general not shown superiority of levothyroxine plus liothyronine combination therapy over levothyroxine monotherapy Some reports suggest a preference of patients for levothyroxine plus liothyronine combination therapy over levothyroxine monotherapy, which might be associated with weight loss Levothyroxine remains the standard treatment modality for hypothyroidism, but levothyroxine plus liothyronine combination treatment might be offered to selected patients as an experimental modality, according to guidelines published in 2012 Abstract Impaired psychological well-being, depression or anxiety are observed in 510% of hypothyroid patients receiving levothyroxine, despite normal TSH levels

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