Psychosomatic Medicine 30:666-681 (1968)
© 1968 American Psychosomatic Society

A Review of Psychoendocrine Research on the Pituitary-Thyroid System

¹ Department of Neuroendocrinology, Division of Neuropsychiatry, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D. C.

At first glance, the present status of psychoendocrine research on the pituitary-thyroid system may appear somewhat confusing. Yet if certain methodological issues are considered critically, the field may not be so unsettled as it first appears. It is perhaps particularly illuminating to view this work in the perspective of the more advanced but similar psychoendocrine research on the adrenal systems. If this is done, several conspicious deficiencies and limitations of the present data are evident, as are some special problems in thyroid physiology which appear to require special handling from an investigative standpoint.

One important deficiency in studies with normal human subjects has been the reliance upon situational criteria of"stress" and upon mean group values, with a relative lack of systematic evaluation of the important and often marked individual differences between subjects in their emotional and defensive reactions to a given situation.

Likewise, studies with psychiatric patients have largely been based upon comparison or "contrast" between groups according to static diagnostic criteria and have often not included assessment of psychological state at the time hormone measurements were made.

In addition, some special problems complicate the experimental evaluation of thyroid activity that were not encountered in work with the adrenal systems and which require special measures in experimental design and data analysis. Perhaps a key issue is that relating to the relatively narrow range of fluctuation in absolute blood thyroid hormone levels. Different standards for judging the significance of changes in hormonal levels in this "tightly regulated" system are apparently indicated, in keeping with the difference in its dynamic characteristics as compared with other endocrine systems. The use of nonparametric methods of data analysis, for example, may be particularly suitable in dealing with this system. It also follows that the error of the biochemical method may assume greater importance here than in work with other endocrine systems. In view of this problem, it appears to be a highly questionable judgment to dismiss changes of 1 to 2 µg.% in PBI or BEI levels as biologically unimportant.

The use of the "normal range" concept as a criterion for judging the biological significance of psychoendocrine responses of the pituitary-thyroid system is probably unsound and has been a misleading and confusing factor in this field. The extensive development of psychoendocrine relationships in the study of the adrenal systems has occurred largely within what might similarly be called the "normal range" of hormonal values.

Taking the above factors into consideration, the following conclusions are suggested.

The study of normal human subjects under stressful conditions indicates that "small" elevations in thyroid hormone levels, of the order of 1 to 2 µg.%--possibly preceded by a transient decrease in some instances--are associated with acute emotional disturbances. The elevation in levels appears to be more marked in hyperthyroid patients.

Longitudinal studies of psychiatric patients suggest similar "small" PBI elevations in disturbed phases as compared with clinically less disturbed phases of illness.

There is general agreement that thyroid responses to emotional stimuli occur in laboratory animals, but the direction of such responses is in question. Generally, small animals such as rats, mice, and rabbits have shown decreases, while larger animals (including primates) have shown increases in thyroid activity in association with acute emotional disturbances. Some evidence has been presented suggesting that bona fide species differences may be involved. Other evidence suggests that the reported discrepancies may be related to the lack of close attention to the time course of the thyroid response to emotional stimuli, and that a biphasic response may be involved. Further experiments will be needed to settle this question.

While the plasma PBI or BEI measurements are probably the most useful indices of thyroid hormone secretion available at present, methodological advances are needed in this field. The recent impressive progress in the radioimmunoassay of peptide and protein hormones offers hope that a reliable method for TSH measurement may soon be available. Meanwhile, it may be helpful if workers in this field include both blood hormone and radioiodine methods in the same study whenever possible. The concurrent measurement of plasma PBI or BEI, plasma ¹³¹PBI, ¹³¹I uptake, ¹³¹ I release rate, ¹³¹I excretion, and inorganic iodine levels should help clarify the question of how closely these various indices correlate and also help to determine under what conditions they may become dissociated. ¹³¹I turnover studies should be of interest. Assessment of the levels of thyroxine-binding protein and of "free" thyroxine may well also be included in this battery of measurements because of recent interest in the role of the protein as a determinant of plasma hormone levels.

Another need in this field is for more extensive investigation not only of acute disturbances and thyroid activity but also of possible relationships between chronic mean basal thyroid hormone levels and personality characteristics--particularly in relation to defensive organization in normal human subjects. Such studies have been among the most intriguing and provocative in recent psychoendocrine research on the pituitaryadrenal cortical system.

While consideration of the methodological and theoretical points discussed above may appear to have some explanatory value and to point to some general conclusions in the field, it is clear that further research is much needed before such conclusions can be regarded as firm. In any event, it certainly seems more defensible at present to regard the findings in this field as inconclusive rather than as negative or seriously conflicting. If the recent advances in psychiatric methodology from the adrenal psychoendocrine fields are used to proper advantage, and if energetic efforts are made to refine endocrine methodology to accommodate the special problems of thyroid physiology, particularly in relation to dynamics, it is likely that a more confident decision may soon be forthcoming concerning the placement of the pituitary-thyroid system in the psychoendocrine category.

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