Congenital Hypothyroidism and Atherosclerosis: An Endocrine Model of Early-Life Cardiovascular Risk

Congenital hypothyroidism (CH) is a common endocrine disorder characterized by thyroid hormone deficiency and has dramatic consequences if diagnosis and treatment are delayed. Although neonatal screening (NNS) and early levothyroxine (L-T4) treatment have markedly improved neurodevelopmental outcomes, evidence suggests that cardiovascular alterations may persist into later life. Thyroid hormones regulate lipid metabolism, endothelial nitric oxide (NO) availability, myocardial relaxation, vascular tone and arterial wall homeostasis. Early clinical studies in patients with CH reported variable lipid and lipoprotein abnormalities, whereas more recent studies have demonstrated endothelial dysfunction, increased arterial stiffness, and elevated carotid intima–media thickness (IMT), even in the absence of classical cardiovascular risk factors. These alterations appear to be associated with cumulative exposure to thyroid-stimulating hormone (TSH) abnormalities rather than isolated biochemical measurements. These findings suggest that CH may affect cardiovascular biology through multiple pathways, including dyslipidemia, endothelial dysfunction, vascular remodeling, and cumulative exposure to thyroid-stimulating hormone abnormalities. This review summarizes the available evidence linking congenital hypothyroidism to early vascular and atherosclerotic changes and discusses its conceptual relationship to familial hypercholesterolemia as another model of early-life cumulative cardiovascular risk.