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Recombinant Human GH Replacement Therapy and Thyroid Function in a Large Group of Adult GH-Deficient Patients: When Does L-T₄ Therapy Become Mandatory?

Institute of Endocrine Sciences, Inc. (S.P., C.G., C.R., M.A., P.B.-P.), University of Milan, Ospedale Maggiore IRCCS, 20122 Milan; Department of Molecular and Clinical Endocrinology and Oncology (G.L.), University Federico II, 80100 Naples; and Department of Medical and Surgical Sciences (M.Z.), University of Padua, 35100 Padua; and Eli Lilly \|[amp ]\| Co. Italia (D.V.), 50100 Florence, Italy

Address all correspondence and requests for reprints to: Paolo Beck-Peccoz, M.D., Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, Pad. Granelli, Via Francesco Sforza, 35; 20122 Milano, Italy. E-mail: . paolo.beckpeccoz{at}unimi.it

Abstract

The effect on thyroid function of GH administration to 66 adult patients with severe GH deficiency was studied. Seventeen patients were euthyroid, and 49 had central hypothyroidism and were adequately treated with L-T₄. Forty patients were assigned to a low recombinant human GH (rhGH) regimen (3 µg/kg body wt·d for 3 months followed by 6 µg/kg body wt·d for another 3 months) and 26 to a higher one (6 µg/kg body wt·d for 3 months followed by 12 µg/kg body wt·d for another 3 months). Serum IGF-I, TSH, free T₄ (FT₄), free T₃ (FT₃), reverse T₃, T₄-binding globulin, and antithyroid autoantibody (TgAb and TPOAb) were measured in basal condition and after 3 and 6 months of therapy.

Normalization of IGF-I levels was obtained after 6-month rhGH treatment in 67% of patients, independently from the dose, whereas a significant reduction in FT₄ and reverse T₃ levels was recorded (P < 0.01), without variations in all the other parameters studied, including serum TSH, FT₃, and T₄-binding globulin circulating levels. Antithyroid autoantibodies were detected in 11 of 66 patients (16.6%).

Eight of 17 (47%) euthyroid subjects and 9 of 49 (18.3%) central hypothyroid patients, despite adequate substitution at baseline, showed FT₄ levels under the normal range at the end of the study. Altogether, 17 of 66 patients (25.7%) worsened their thyroid function.

This study shows that GH deficiency masks in a consistent number of adult patients a state of central hypothyroidism. Therefore, during rhGH treatment, a careful monitoring of thyroid function is mandatory to start or adjust L-T₄ substitutive therapy.

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