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Evaluation of the Adequacy of Levothyroxine Replacement Therapy in Patients with Central Hypothyroidism¹

Institute of Endocrine Sciences (L.P., S.G., P.B.-P.), University of Milan, Ospedale Maggiore IRCCS, Istituto Auxologico Italiano IRCCS, and Istituto Clinico Humanitas, Milan; the Department of Endocrinology (E.F., G.T.), University La Sapienza, Rome; and the Department of Experimental Medicine (E. F., M.-L.J.-R.), University of L’Aquila, L’Aquila, Italy

Address all correspondence and requests for reprints to: Paolo Beck-Peccoz, M.D., Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano-Milan, Italy. E-mail: paolo.beck-peccoz{at}humanitas.it

As there are few data on the evaluation of the adequacy of levothyroxine (L-T₄) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T₄ therapy. Samples were taken before the daily administration of L-T₄. In all patients off therapy, clinical hypothyroidism and low levels of free T₄ (FT₄) were observed, whereas values of FT₃, total T₄, and total T₃ were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T₄ withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T₄ replacement therapy, 32 patients had circulating levels of FT₄ and FT₃ and indexes within the normal range with a mean L-T₄ daily dose of 1.5 ± 0.3 µg/kg BW. Despite normal serum FT₄, 3 patients had borderline high values of FT₃ and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT₄/FT₃ levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T₄ daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients.

In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT₄ concentrations. In the evaluation of the adequacy of L-T₄ replacement therapy, both FT₄ and FT₃ serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients.

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