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In primary thyroid disease, overproduction of
thyroid hormones results in a lower TSH secretion; vice versa,
underproduction will result in an increased TSH secretion. From
longitudinal observations in hyperthyroid and hypothyroid
patients in whom euthyroidism is restored (10), and from subacute
experiments in healthy subjects in whom hyperthyroidism or slight
hypothyroidism is induced by the administration of thyroxine or
potassium iodide respectively (11), it can be deduced that there
exists an intra-individual log-linear
relationship between TSH and FT4, as depicted by a straight line:
the working- point of the pituitary-thyroid axis moves along this
line, upwards in case of hypothyroidism and downwards in case of
hyperthyroidism (Figure 2). The line itself can be viewed as the
set-point of the pituitary-thyroid axis in that individual. In
primary hypothyroidism and hyperthyroidism nothing is wrong with
the setpoint which functions appropriately; it is just the
working-point which changes. Variations in setpoint between
individuals can be represented as parallel lines, different in
position but not in slope.
Figure 2:
The presence of significant inter-individual variation in the setpoint of the pituitary-thyroid axis raises conceptual problems with the current univariant approach in interpreting thyroid function tests. The position of the working point of an individual influences the maximally allowed changes of thyroid function tests within the conventional normal range before they are labelled as abnormal. Some patients will be classified as abnormal after small changes in thyroid hormone production, others only after much greater changes. In other words, an equal fall in thyroid hormone production resulting in the same FT4 values, will adjust serum TSH to values either within or just above the normal range depending on the position of the original working-point (Figure 3). Conversely, a slightly increased serum TSH can be the result of a rather small decrease in thyroid hormone production in one patient but of a relatively larger decrease in another patient. It is conceivable that the latter but not the former patient will have subtle classical signs and symptoms of thyroid hormone deficiency. This line of reasoning would resolve the question why some patients with subclinical thyroid dysfunction are symptomatic whereas others are not. The use of graphical bivariate representation of reference ranges would diminish this kind of discrepancy between biochemical and clinical evaluation of the thyroid condition, allowing greater diagnostic accuracy in borderline cases (12). Figure 3
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