Because of lack of well-documented laboratory criteria, we assessed the usefulness of measuring free thyroxine (FT4) levels for monitoring levothyroxine replacement therapy in patients with central hypothyroidism. This consisted of a retrospective review from 1991-1997 of patient profiles extracted into a Macintosh 4th Dimension data base from the medical information system at a tertiary care biomedical research facility. Information was also retrieved from medical records of 135 ambulatory patients treated by 42 endocrinology practitioners, and 52 ambulatory patients treated by 20 endocrinology practitioners for central and primary hypothyroidism, respectively. Patient profiles were reviewed for most recent thyroid function test results and levothyroxine dosing information. Of 112 (83%) patients with central hypothyroidism who had FT4 levels within the laboratory's reference interval, only 2 had a dosage change. The FT4 concentration was concordant with physician-assessed thyroid status in 65 (82%) of 79 patients (95% CI 72-90, p<0.02) for whom clinical assessment was available in medical records. Thyrotropin, total thyroxine, and triiodothyronine levels were not significantly associated with clinical status (p>0.12) in patients with central hypothyroidism. Despite similar demographic and levothyroxine dosing profiles, patients with central hypothyroidism had significantly lower serum FT4 and thyrotropin concentrations than those with primary hypothyroidism. The appropriateness of levothyroxine replacement therapy in most patients with central hypothyroidism is reflected by a normal FT4 concentration measured with a valid assay. Whether midnormal or upper normal values are necessary for optimal therapy, and whether the therapeutic goal should be different in children than in adults, require prospective studies with independent, objective assessment of thyroid status.

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