The total loss of functional thyroid tissue is particularly challenging for a patient. It leaves the patient in a state of athyroidism and entirely dependent on external hormone supply. It also breaks the homeostatic regulation of the hypothalamic–pituitary–thyroid axis, especially with respect to thyroid-stimulating hormone (TSH) signalling, FT3 stability, and FT3 homeostasis [1, 2]. The pathophysiology of this condition has been explored and explained in preceding chapters on relational stability and hypothalamic–pituitary–thyroid regulation. Main causes for an irreversible loss of thyroid function are a long history of thyroid autoimmune disease with progressive destruction of thyroid tissue and ablative treatments such as total thyroidectomy and radioiodine administration for malignant or less frequently benign thyroid disease.