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Health Status, Mood, and Cognition in Experimentally Induced Subclinical Hypothyroidism

Divisions of Endocrinology, Diabetes, and Clinical Nutrition (M.H.S., K.G.S.) and Biostatistics (N.E.C.) and Department of Behavioral Neurosciences (P.C., J.S.J.), Oregon Health and Science University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Mary H. Samuels, M.D., CR107, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239. E-mail: samuelsm{at}ohsu.edu.

Objective: The objective of the study was to determine whether subclinical hypothyroidism causes decrements in health status, mood, and/or cognitive function.

Design: This was a double-blinded, randomized, crossover study of usual dose L-thyroxine (L-T4) (euthyroid arm) vs. lower dose L-T4 (subclinical hypothyroid arm) in hypothyroid subjects.

Patients: Nineteen subjects on L-T4 therapy for primary hypothyroidism participated in the study.

Measurements: Subjects underwent measurements of health status, mood, and cognition using validated instruments: Short Form 36, Profile of Mood States, and tests of declarative memory (paragraph recall, complex figure), working memory (N-back, subject ordered pointing, digit span backward), and motor learning (pursuit rotor). The same measures were repeated after 12 wk on each of the study arms.

Results: Mean TSH levels increased to 17 mU/liter on the subclinical hypothyroid arm (P < 0.0001). Mean free T₄ and free T₃ levels remained within the normal range. The Profile of Mood States fatigue subscale and Short Form 36 general health subscale were slightly worse during the subclinical hypothyroid arm. Measures of working memory (N-back, subject ordered pointing) were worse during the subclinical hypothyroid arm. These differences did not depend on mood or health status but were related to changes in free T₄ or free T₃ levels. There were no decrements in declarative memory or motor learning.

Conclusions: We found mild decrements in health status and mood in L-T4-treated hypothyroid subjects when subclinical hypothyroidism was induced in a blinded, randomized fashion. More importantly, there were independent decrements in working memory, which suggests that subclinical hypothyroidism specifically impacts brain areas responsible for working memory.

This article has been cited by other articles:

				M. H. Samuels, K. G. Schuff, N. E. Carlson, P. Carello, and J. S. Janowsky Health Status, Mood, and Cognition in Experimentally Induced Subclinical Thyrotoxicosis J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1730 - 1736. [Abstract] [Full Text] [PDF]