Treatment of hypothyroidism relies on the principle of hormone substitution through external administration of thyroid hormones when the patient’s own thyroid gland can no longer produce them in sufficient quantities [1, 2]. This permits the normal functioning of the many thyroid hormone-dependent reactions and metabolic actions. Physiologically, the human thyroid gland produces mainly two thyroid hormones, a large amount of T4 and a much lesser amount of T3 (Chap. 3 ). Both hormones are stored in the follicular structure of the gland to be readily available and released on-demand in a controlled way (Chap. 5 ). The storage capability of the thyroid gland is different from other endocrine glands, such as the adrenals or testes, which cannot rely on stored hormone depots. This unique feature of the thyroid gland makes the supply of the body with thyroid hormones less dependent on nutritional variations in iodine supply, provisional and through its regulation anticipatory of demand. In the thyroid system, the two main hormones, T4 and T3, have different properties and differentiated roles. While T4 is exclusively synthesised by the thyroid, dependent on appropriate and controlled glandular stimulation by the pituitary hormone, thyroid-stimulating hormone (TSH), T3 is only partly synthesised there and generated to a much larger extent locally in many other tissues via enzymatic monodeiodination of T4. Notably, the proportion of intra-thyroidal and extra-thyroidal T3 production is not fixed, as often falsely assumed, but adapts to different conditions [3]. In this regard, an important study has been carried out in rats [4]. With their fully functioning thyroid still in place, the animals were even able to survive under experimental conditions of a deficiency in all three types of deiodinases and the total loss of extra-thyroidal T3 generation by the enzymes [4]. Given the conversion of T4 to T3 and activation of the former to a molecule of enhanced potency, T4 is regarded as a precursor to T3. The intra-thyroidal formation of T3 from its precursor T4 is subject to feed-forward regulation by pituitary TSH, as is thyroidal T3 secretion [5–9]. The pleiotropic signalling through TSH provides unexpected system-level functionality to the hypothalamic–pituitary–thyroid axis regulation [9]. It supports robustness of the system, allowing for the maintenance of FT3 homeostasis despite changes in the availability of its precursor FT4. While the actions of FT4 and TSH oppose each other in the regulation of the hypothalamic–pituitary–thyroid axis, they combine and join forces to maintain FT3 concentration at a homeostatic level [9]. The clinical relevance has already been discussed when introducing the concept of relational stability (see ibid). This design of control is not unique to hypothalamic–pituitary–thyroid regulation, but more generally operative in growth control via two hormones (human growth hormone and insulin-like growth factor 1) and cellular circuits with incomplete feed-forward loops of control by “paradoxical” components [10].

Treatment of Hypothyroidism

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发表日期：

2025年

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Rudolf Hoermann,
Johannes W. Dietrich

摘要

Treatment of hypothyroidism relies on the principle of hormone substitution through external administration of thyroid hormones when the patient’s own thyroid gland can no longer produce them in sufficient quantities [1, 2]. This permits the normal functioning of the many thyroid hormone-dependent reactions and metabolic actions. Physiologically, the human thyroid gland produces mainly two thyroid hormones, a large amount of T4 and a much lesser amount of T3 (Chap. 3 ). Both hormones are stored in the follicular structure of the gland to be readily available and released on-demand in a controlled way (Chap. 5 ). The storage capability of the thyroid gland is different from other endocrine glands, such as the adrenals or testes, which cannot rely on stored hormone depots. This unique feature of the thyroid gland makes the supply of the body with thyroid hormones less dependent on nutritional variations in iodine supply, provisional and through its regulation anticipatory of demand. In the thyroid system, the two main hormones, T4 and T3, have different properties and differentiated roles. While T4 is exclusively synthesised by the thyroid, dependent on appropriate and controlled glandular stimulation by the pituitary hormone, thyroid-stimulating hormone (TSH), T3 is only partly synthesised there and generated to a much larger extent locally in many other tissues via enzymatic monodeiodination of T4. Notably, the proportion of intra-thyroidal and extra-thyroidal T3 production is not fixed, as often falsely assumed, but adapts to different conditions [3]. In this regard, an important study has been carried out in rats [4]. With their fully functioning thyroid still in place, the animals were even able to survive under experimental conditions of a deficiency in all three types of deiodinases and the total loss of extra-thyroidal T3 generation by the enzymes [4]. Given the conversion of T4 to T3 and activation of the former to a molecule of enhanced potency, T4 is regarded as a precursor to T3. The intra-thyroidal formation of T3 from its precursor T4 is subject to feed-forward regulation by pituitary TSH, as is thyroidal T3 secretion [5–9]. The pleiotropic signalling through TSH provides unexpected system-level functionality to the hypothalamic–pituitary–thyroid axis regulation [9]. It supports robustness of the system, allowing for the maintenance of FT3 homeostasis despite changes in the availability of its precursor FT4. While the actions of FT4 and TSH oppose each other in the regulation of the hypothalamic–pituitary–thyroid axis, they combine and join forces to maintain FT3 concentration at a homeostatic level [9]. The clinical relevance has already been discussed when introducing the concept of relational stability (see ibid). This design of control is not unique to hypothalamic–pituitary–thyroid regulation, but more generally operative in growth control via two hormones (human growth hormone and insulin-like growth factor 1) and cellular circuits with incomplete feed-forward loops of control by “paradoxical” components [10].