Disease relevance of Hyperthyroxinemia

• These cases of euthyroid familial hyperthyroxinemia due to an abnormal thyroid hormone-binding protein show that an elevated serum thyroxine level or free thyroxine index is not always sufficient to confirm the presence of thyrotoxicosis [1].
• Methods to identify the plasma T4-binding abnormalities that can cause euthyroid hyperthyroxinemia were evaluated in patients with excess T4-binding globulin, familial dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, and autoantibody binding of T4 [2].
• Alterations in TTR structure can manifest clinically as familial amyloidotic polyneuropathy or euthyroid hyperthyroxinemia [3].
• In spite of the presence of TSH-R Ab, SCID-TH from GD patients did not show persistent hyperthyroxinemia, presumably because destructive thyroiditis may be occurring in the grafted tissue, with decreasing levels of TSH-R Ab [4].
• Unfortunately, hyperthyroxinemia due to FDH may be confused with hyperthyroidism or thyroid hormone resistance syndromes, prompting repeated unnecessary laboratory testing and possibly even inappropriate treatment (1,3,6,7) [5].

High impact information on Hyperthyroxinemia

• Familial euthyroid hyperthyroxinemia resulting from increased thyroxine binding to thyroxine-binding prealbumin [6].
• A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia [7].
• In this familial syndrome characterized by eumetabolic hyperthyroxinemia, the alteration of thyroid hormone metabolism seems to involve primarily the partition of T4 between the intra- and extracellular spaces [8].
• Thyroxine-binding globulin, hyperthyroxinemia and hepatocellular carcinoma [9].
• The lower D1 levels are paralleled by a decreased normal-sized dio1 mRNA and hyperthyroxinemia [10].

Chemical compound and disease context of Hyperthyroxinemia

• Familial hyperthyroxinemia due to abnormal thyroid hormone binding [11].
• Propranolol-induced hyperthyroxinemia [12].
• The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated [13].
• Recently, a transthyretin variant, TTR Met 119, in which methionine substitutes for threonine 119, a component of the protein's iodothyronine binding site, was identified in individuals with transient euthyroid hyperthyroxinemia [14].
• The affinity of albumin for T4 is increased by histidine substitution for arginine 218 in the most common form of dysalbuminemic hyperthyroxinemia [15].

Biological context of Hyperthyroxinemia

• We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia [16].

Anatomical context of Hyperthyroxinemia

• Euthyroid hyperthyroxinemia and thyroxine-binding prealbumin excess in islet cell carcinoma [17].
• These results indicate a deleterious effect of hyperthyroxinemia on insulin controlled glucose metabolism in fat cells [18].
• RESULTS: Two diagnostic groups were identified: Hyperthyroxinemia secondary to binding abnormalities (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13) [19].

Gene context of Hyperthyroxinemia

• In a family expressing euthyroid hyperthyroxinemia, an increased association of plasma thyroxine (T4) with transthyretin (TTR) is transmitted by autosomal dominant inheritance and is secondary to a mutant TTR molecule with increased affinity for T4 [7].
• SCID-TH from GD and HT patients showed transient hyperthyroxinemia, peaking at 2 weeks; these values were significantly higher [free T4, 6.48 +/- 0.90 and 5.50 +/- 0.77 pmol/L (mean +/- SE), respectively; P < 0.05] than SCID-TH from normal controls (2.5 +/- 0.24) [4].
• Immunization with the extracellular domain of TSH receptor (TSHR) led to the development of hyperthyroxinemia in BALB/cJ, but not C57BL/6J, SJL/J, and B10.BR, mice [20].
• Thyrotropin receptor-specific antibodies in BALB/cJ mice with experimental hyperthyroxinemia show a restricted binding specificity and belong to the immunoglobulin G1 subclass [20].
• We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level [21].

References