Hypothyroidism compensated

A rise in the TSH level is the first evidence of primary hypothyroidism. Many patients have a free T4 level within the normal range (compensated hypothyroidism) and few, if any, symptoms of hypothyroidism. As the disease progresses, the free T4 concentration drops below the normal level. The T3 concentration is often maintained in the normal range despite a low T4. Antithyroid peroxidase antibodies and antithyroglobulin antibodies are likely to be elevated. The RAIU is not a useful test in the evaluation of hypothyroidism because it can be low, normal, or even elevated. 

A rise in the TSH level is the first evidence of primary hypothyroidism. Many patients have a free T4 level within the normal range (compensated hypothyroidism) and few, if any, symptoms of hypothyroidism. As the disease progresses, the free T4 concentration drops below the normal level. 

Functionally, the state may be compensated up to a certain degree of iodine deficiency and for a considerable period of time, described in clinical terms as euthyroid diffuse or nodular goiter. Functional failure follows only in the presence of severe iodine deficiency, and hypothyroidism may then develop. Much more frequently and somewhat paradoxically, hyperthyroidism ensues after many years of iodine depletion. Rarely, hyperthyroidism may be found in cases of diffuse goiter, which are then termed as diffuse thyroid autonomy. Fiowever, hyperthyroidism frequendy occurs in conjunction with uninodular (toxic adenoma) and multinodular goiters (toxic multinodular goiter). 

It is now becoming increasingly recognized that Ts hypersecreting states other than Ta-thyrotoxicosis exist and can occur in a variety of clinical situations. The common denominator is a slowly decreasing thyroid reserve, which is compensated for, either fully or in part, by a Ts hypersecretion, which is probably TSH mediated. The total T4 levels are either low normal or definitely subnormal, and yet none of these patients show any marked evidence of clinical hypothyroidism. 

Estrogens increase thyroxine binding-globulin. In women with normal thyroid function this does not alter free thyroxine levels or TSH levels, as the thyroxine secretion can increase to accommodate the changes. However, in women with hypothyroidism who cannot compensate for the increased thyroxine binding, decreased free thyroxine and therefore increased TSH can result. 

There seem to be no reports of adverse effects in other patients given both drugs and the evidence for this interaction is by no means conclusive. Although rifampicin can affect thyroid hormones, it appears that healthy individuals can compensate for this. Since hypothyroid patients may not be able to compensate in the same way, bear this interaction in mind if rifampicin is given to a patient taking levothyroxine. 

If we may extrapolate from these results to the clinical situation, we conclude that maintenance of optimal intracellular T3 concentrations in the central nervous system requires T4 as a substrate and a series of adaptations in the metabolism of this prohormone and T3, which then compensates for the plasma hypothyroxinemia. To the extent that the compensatory changes described in the cerebral cortex of the hypothyroid rat do not occur in the human, a reduction of serum T4 in iodine deficient persons could present a significant threat to the thyroid status of the cerebral cortex, even if serum T3 remained at normal concentrations. There are no data with respect to the presence of a local T4 to T3 conversion system in the human central nervous system. However, the similarity of the responses of the pituitary-thyroid axis to hypothyroidism and iodine deficiency in the rat and man suggests that the Type 11 deiodinase is common to both species (28,43). Presumably then, the concepts regarding intracerebral thyroid hormone metabolism derived from those experiments in the rat are also relevant to man. 

The LID fetuses developed goiter, and their thyroidal total iodine was 4.7 % of that of LID + I fetuses. The concentrations of T4 and T3 in different embryonic and fetal samples are shown in Figs. 8 and 9, where they are compared to data from age-paired samples obtained from C and T dams. Before onset of fetal thyroid function (11-day-old embryotrophoblasts and 17-day old fetuses) T4 concentrations are decreased by LID to a degree comparable to that of concepta taken from T mothers. T3 concentrations did not differ initially from those of the LID + I group. By 17 gd, however, T3 concentrations were lower both in the fetus, and placenta (not shown). Once fetal thyroid function starts, important differences become apparent between fetuses from T and LID dams. The activated secretion of T4 and T3 by the thyroid in fetuses from T mothers is able to compensate for previous differences related to maternal hypothyroidism, at least as far as the brain is concerned. But this is not possible for fetuses faced with a very low iodine supply, and cerebral T3 is quite low. Similar results were later obtained in another experimental series ... 

Simple goitre accompanied by hypothyroidism may arise when there is a deficiency of iodine in the diet. This is due usually to a faulty environment. A compensational hypertrophy of the gland endeavours unsuccessfully to manufacture sufficient autacoid from inadequate material. 

---