When it comes to hyperthyroxinemia, how is it possible for TSH to be normal when there is an elevated thyroxine concentration? What I know so far is that it is caused by a mutation in the Human serum albumin (P02768)that carries normally around 10% of the thyroxine.The mutation apparently makes it have a higher affinity for thyroxine, but how does it allow the TSH levels to remain normal?
Since you're asking about hyperthyroxinemia with normal TSH serum levels, I suppose you're talking about euthyroid hyperthyroxinemia.
In euthyroid hyperthyroxinemia, the serum T4 and T3 concentrations are increased, but the TSH concentration remains normal. Besides that, there are normally no clinical signs.
The cause of that increase, as you explain in your own question, is a mutation in a transporter protein (like TBG), or an increase in their concentrations (which can happen in patients with hepatocarcinoma, for instance).
However, the free T4 concentration remains the same, and that is the important value for the negative feedback mechanism that regulates the concentration of TSH:
The euthyroid status of subjects with FDH has been confirmed by normal TSH response to TRH, normal free T4 concentration measured by equilibrium dialysis using appropriate buffer systems, normal T4 production rate and normal serum sex hormone-binding globulin concentration.
Thus, without an increase in free T4 levels, there will be no drop in the TSH concentration.
Differential diagnoses of hyperthyroxinaemia with non-suppressed TSH levels include secondary or tertiary hyperthyroidism (e.g. due to TSH-secreting pituitary adenoma, resistance to thyroid hormone or paraneoplastic TRH production, respectively, all of them being very rare) and transient activation of the feedback loop in situations of type 2 thyroid allostasis1. In the context mentioned by you, elevated concentrations of T4 are most likely caused by increased plasma protein binding (which leaves free T4 normal)2.
Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH and Dietrich JW (2017) Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Front. Endocrinol. 8:163. PMID 28775711 doi 10.3389/fendo.2017.00163
Bianchi R, Iervasi G, Pilo A, Vitek F, Ferdeghini M, Cazzuola F, Giraudi G. Role of serum carrier proteins in the peripheral metabolism and tissue distribution of thyroid hormones in familial dysalbuminemic hyperthyroxinemia and congenital elevation of thyroxine-binding globulin. J Clin Invest. 1987 Aug;80(2):522-34. PMID 3112186.