Clinical meaning
Hypothyroidism is insufficient thyroid hormone production resulting in a hypometabolic state. Primary hypothyroidism (95% of cases) involves thyroid gland failure with elevated TSH (pituitary compensatory response) and low free T4. Hashimoto thyroiditis (chronic autoimmune lymphocytic thyroiditis) is the most common cause in iodine-sufficient areas — anti-TPO antibodies mediate lymphocytic infiltration and destruction of thyroid follicular cells. Other primary causes include: post-radioactive iodine ablation, post-thyroidectomy, iodine deficiency (most common cause worldwide), medications (amiodarone, lithium, interferon-alpha, tyrosine kinase inhibitors), radiation therapy to head/neck, and subacute/postpartum thyroiditis (transient hypothyroid phase). Secondary (central) hypothyroidism (<5%) involves pituitary TSH deficiency — TSH is LOW or inappropriately normal with low FT4. Subclinical hypothyroidism is elevated TSH with normal FT4/FT3 — treat if TSH >10 or if symptoms present with TSH 5-10 and positive anti-TPO antibodies. Thyroid hormones regulate basal metabolic rate by increasing oxygen consumption and heat production (upregulating mitochondrial activity), enhancing catecholamine receptor sensitivity (affecting cardiac output), stimulating protein synthesis, and promoting lipid metabolism (hypothyroidism causes hypercholesterolemia). Myxedema coma is the severe, life-threatening form: hypothermia, hypoventilation, hypoglycemia, hyponatremia, altered mental status — mortality 30-60% even with treatment. Treatment: IV levothyroxine, IV hydrocortisone (must treat possible concurrent adrenal insufficiency), passive rewarming, ventilatory support.