Transthyretin ∞ Area

Transthyretin

Meaning

Transthyretin (TTR) is a protein synthesized primarily by the liver. It functions as a crucial carrier for thyroid hormones, specifically thyroxine (T4), and for retinol (Vitamin A) complexed with retinol-binding protein (RBP). Its presence is vital for appropriate transport and distribution of these essential substances throughout the body.

Context

Within human physiology, transthyretin plays a critical role in systemic T4 delivery from bloodstream to various tissues, ensuring proper thyroid hormone availability for metabolic regulation. It also facilitates Vitamin A distribution, essential for vision, immune function, and cellular differentiation. Its synthesis occurs predominantly in the liver, with lesser amounts produced in choroid plexus and retina.

Significance

Transthyretin levels can indicate nutritional status, liver function, and systemic inflammation clinically. Dysregulation of TTR is central to transthyretin amyloidosis, where misfolded TTR proteins accumulate as amyloid deposits in organs like the heart and nerves, causing organ dysfunction. Understanding TTR’s role helps clinicians diagnose and manage these conditions.

Mechanism

Transthyretin is a homotetramer, consisting of four identical protein subunits that assemble into a stable structure. This structure provides binding sites for thyroxine and retinol-binding protein, enabling reversible transport and cargo release at target cells. In amyloidosis, specific genetic mutations or age-related changes destabilize this tetrameric structure, causing dissociation into monomers that misfold and aggregate into amyloid fibrils.

Application

Clinically, transthyretin levels are occasionally assessed as a marker of protein-calorie malnutrition or an acute phase reactant in inflammatory states, though their utility is debated. Genetic testing for TTR mutations is key for diagnosing hereditary transthyretin amyloidosis. Therapeutic strategies targeting TTR stabilization or degradation are now employed to manage this progressive disease, including pharmacological interventions preventing TTR dissociation or reducing its synthesis.

Metric

Serum transthyretin concentration, typically reported in milligrams per deciliter (mg/dL), is the primary metric for assessing its circulating levels. For amyloidosis, diagnostic methods include genetic sequencing for TTR mutations and mass spectrometry to detect TTR amyloid deposits in tissues. Cardiac imaging, such as echocardiography or MRI, evaluates organ involvement; biopsies confirm amyloid deposition.

Risk

Transthyretin, while physiological, carries risks through genetic variants or its misfolding propensity. The main risk is transthyretin amyloidosis, causing progressive organ damage, especially to the heart (cardiomyopathy), nervous system (neuropathy), and kidneys. Without timely diagnosis and intervention, this condition leads to substantial morbidity and mortality. Misinterpretation of TTR levels in other contexts can also result in inaccurate clinical assessments.