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Patterns of Recovery of the Hypothalamic-Pituitary-Thyroid Axis in Patients Taken off Chronic Thyroid Therapy

Endocrine Research Laboratory, Medical and Research Services, Veterans Administration Wadsworth Hospital Center Los Angeles California 90073
Department of Medicine, University of California Los Angeles California 90024

Send reprint requests to Jerome M. Hershman, M.D., Wadsworth VA Hospital, Los Angeles, California 90073.

To determine the patterns of recovery of the hypothalamic-pituitary-thyroid axis following long-term thyroid hormone therapy, TRH tests were performed on 8 euthyroid nongoitrous patients, 5 euthyroid goitrous patients, and 5 hypothyroid patients while they were taking full doses of thyroid hormone and 3, 7, 10, 14, 17, 21, 28, 35, 42, 49, and 56 days after stopping it. Serum TSH, T₃, and T₄ were measured before and at multiple intervals over a 4-h period after giving 500 µg TRH iv. In euthyroid non-goitrous patients, the mean duration of suppressed TSH response to TRH (maximum TSH < 8 µU/ml) was 12 ± 4 (SE) days after stopping thyroid hormone and the mean time to recovery of normal TSH response to TRH (maximum TSH > 8 µU/ml) was 16 ± 5 days. None of the euthyroid nongoitrous patients ever hyperresponded to TRH; their average maximal TSH was 24.5 ± 2.2 µU/ml. Serum T₄ fell below normal in 4 euthyroid nongoitrous patients, reaching lowest values at 4 to 28 days. While serum T₄ was low, TSH was subnormal. Normal increments of T₄ and T₃ after TRH occurred at 19 ± 5 and 22 ± 6 days, respectively.

In the 5 goitrous patients, patterns of recovery of pituitary and thyroid function assessed by the same parameters were much less consistent. In the 5 hypothyroid patients, the mean duration of suppressed basal TSH and suppressed TSH was 13 ± 3 days; mean time to attain a supranormal basal TSH (>8 µU/ml) was 16 ± 4 days and to reach a supranormal TSH (>38 µU/ml) after TRH was 29 ± 8 days.

Following prolonged thyroid therapy in euthyroid patients, recovery of normal TSH responsiveness to TRH preceded recovery of the normal T₃ and T₄ response to TRH by 3 to 6 days. Basal serum TSH may be used to differentiate euthyroid from hypothyroid patients 35 days after withdrawal of thyroid therapy; the response to TRH does not improve this differentiation.

Supported by VA Research Grant 3590–02, USPHS Research Grants HD-7181 and AM-16155, and NIH Career Development Award IK04 AM 70225 (Dr. Chopra).

Received December 6, 1974.

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