Special Aspects of Hypothyroidism: Mild Hypothyroidism, Metabolic Insufficiency & Decreased Thyroid Reserve


The problem of mild hypothyroidism is one that has long vexed both the physician and the clinical physiologist. Until recently, it was uncertain that such a clinical state did in fact occur; this is now accepted. It is highly probable that the greatest proportion of TH therapy administered in the United States is used in treating what is thought to be mild rather than severe thyroid insufficiency. As will become evident, it is the authors' view that, in most instances, the disorders being treated are not truly thyroidal in origin or at least have not been conclusively shown to be so. From the evolution of hypothyroidism in patients with Hashimoto's disease or progressive thyroprivic hypothyroidism, the clinical picture resulting from clearly demonstrable but incomplete thyroid hormone deficiency can be derived. Symptoms include mild lassitude, fatigue, slight anemia, constipation, apathy, slight cold intolerance, menstrual irregularities, inability to conceive, dry skin, some loss of hair, and slight to moderate weight gain. These symptoms, however, are not pathognomonic of hypothyroidism since they also occur either singly or in varying combinations in other disorders of organic or psychogenic origin. With regard to the latter, they constitute the typical picture of the commonly encountered "tired housewife syndrome." Needless to say, similar symptoms are also encountered in single women or even in men.

Many patients with such complaints have been treated with thyroid hormones. Frequently, adequate laboratory documentation of TH deficiency is lacking, or at most, a moderately low BMR is demonstrable. The response to TH therapy is sometimes gratifying, at least initially, but often symptomatic improvement disappears after time, unless the dose is increased. In this way, the total dosage progressively increases until the amounts given exceed those required for complete hormone replacement in frank myxedema. Eventually, even such large doses may fail to alleviate the symptoms. This alone suggests that the symptoms do not arise from deficiency of TH. Some patients report that omission of a single dose of TH results in a rapid emergence (often within hours) of the previous symptoms and that these are equally rapidly relieved by a single dose. These responses are inconsistent with the time of onset and duration of action of thyroid hormones.

As indicated earlier, patterns of thyroid dysfunction have not, by and large, been defined in the majority of patients with the foregoing clinical course. Efforts to do so have led to the suggestion that there may be a type of disturbance in TH economy in which the majority of laboratory function tests are normal. This suggested syndrome, about which much has been written, has been termed metabolic insufficiency or nonmyxedematous hypometabolism. Here, the foregoing symptoms are present to variable degrees. The BMR is by definition decreased (usually slightly to moderately), but evidence of thyroid hypofunction, as judged from the serum T4 concentration or thyroid I[131] uptake, is lacking. It was suggested that the underlying abnormality in such patients is an inability of the tissues to respond to T4, either endogenous or exogenous, while responsiveness to T3 is retained: hence treatment with T3 was advocated. From the outset, it seemed unlikely that the majority of patients ascribed to this category could be suffering from such a defect, since one would have expected compensatory goitrogenesis and thyroid hyperfunction if supplies of hormone to the tissues were inadequate. Neither of these findings was present, however. Moreover, it has been shown in double-blind studies that, in patients satisfying the criteria for the diagnosis of metabolic insufficiency, the symptomatic response to placebo is at least as good as that to T3 (Levin, 1960; Sikkema, 1960). Hence there appears to be no reason at present to retain the concept of such a syndrome or to treat its supposed symptom complex with T3. Studies of the rate of peripheral conversion of T4 to T3 in patients with a typical clinical picture will be required to ascertain whether such a syndrome exists.

Despite the foregoing, it is clear that true mild hypothyroidism does exist. In view of the relatively nonspecific way in which it is clinically manifest, it is mandatory that the diagnosis be adequately documented. This not only will avoid administration of intrinsically ineffective therapy but also will tend to prevent overlooking the true cause of the patient's symptoms. Hypothyroidism resulting from peripheral refractoriness to adequate amounts of hormone, if it exists at all, must be exceedingly rare. Hence mild hypothyroidism results from incomplete failure of TH production. This may lead to laboratory values that are at the lower limit of or still within the normal range. Often only the BMR is slightly lowered, but the serum cholesterol concentration is occasionally increased. To the extent that production of TH is insufficient, the endogenous TSH mechanism must be activated and the serum TSH concentration increased, as is the serum T3 concentration not infrequently. As a result, the degree of endogenous stimulation of the thyroid must be increased, and little, if any, further stimulation would follow the administration of exogenous TSH. Accordingly, an increased serum TSH concentration or a subnormal response to exogenous TSH will permit the diagnosis of mild hypothyroidism due to "decreased thyroid reserve" to be made on the basis of objective criteria. In practice, such patients usually have Hashimoto's disease or have had partial thyroid ablation by surgery or radioiodine. In the remaining instances, the patients may be presumed to be in an early stage of primary thyroprivic hypothyroidism. In such cases, the response to TH is as would be expected, in that the patients respond well to small doses and the response is maintained. Nevertheless, full replacement doses are usually given, because the underlying disorder is generally progressive.

Not infrequently, the physician is confronted with a patient in whom the diagnosis of hypothyroidism, often mild, has already been made, and the patient has been given replacement therapy. In this circumstance, it is impossible to determine from the clinical or laboratory findings whether TH replacement is truly required, since a normal thyroid would have been suppressed. Often, a strong indication that the patient is not truly hypothyroid can be obtained from the nature of his initial complaints or from peculiarities in the response to treatment, as already described. Documentation of true thyroid insufficiency can generally be achieved by two means. First, TH can be withdrawn and the functional state of the thyroid assessed some time later. When the thyroid is intrinsically normal, the I[131] uptake returns within a few weeks to normal or elevated values; the serum T4 concentration may be low for a time but will return to normal. The serum cholesterol remains essentially unchanged in contrast to the increase that occurs in true hypothyroidism. Although patients become psychologically dependent upon the medication and expect a return of symptoms when it is withdrawn, this can often be forestalled by firm reassurance to the contrary. Alternatively, TH therapy may be continued and the intrinsic functional capacity of the thyroid assessed with exogenous TSH, as has been described earlier. A brisk response suggests that no underlying thyroid disorder exists.

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