Is an isolated TSH elevation in chronic nonthyroidal illness "subclinical hypothyroidism"?

Context: Elevated TSH with normal T4 frequently occurs with chronic kidney, liver, and heart diseases. Whether isolated TSH elevations represent mild thyroid gland failure has not been established.

Evidence Acquisition: PubMed was searched for longitudinal studies in chronic heart, liver, or kidney disease documenting persistent isolated TSH elevations or progression to overt hypothyroidism.

Evidence Synthesis: Four articles met inclusion criteria. In 16 end-stage renal failure patients, four had isolated TSH elevations. All normalized within 14 months. In 452 systolic heart failure patients, 20 had isolated TSH elevations, five of 20 were persistent, and none progressed to overt hypothyroidism within 6 months. In 207 untreated chronic hepatitis C patients, 12 had isolated TSH elevations and four had increased TSH with reduced free T4; all were female, and 14 had positive antithyroid antibodies. After 1 year, two of 12 developed "clinical hypothyroidism." In 72 chronic hepatitis C patients, nine females had positive antithyroid antibodies. Two antibody-negative patients had TSH 5-6 mU/L with reduced free T4. After 1 year, three of four with positive antithyroid antibodies and baseline TSH < 4 mU/L had elevated TSH with reduced free T4.

Conclusions: In chronically ill patients, there is inadequate evidence to determine: 1) that isolated TSH elevations usually persist or progress to overt hypothyroidism; 2) the etiology and clinical significance of isolated TSH elevations; and 3) whether levothyroxine therapy is indicated for persistent isolated TSH elevations. Thus, isolated TSH elevations in chronic renal, cardiac, or liver diseases have not been documented to indicate mild thyroid gland failure.