primary hypothyroidism
Summary
Primary hypothyroidism is thyroid hormone deficiency caused by dysfunction of the thyroid gland itself, resulting in low T3/T4 with compensatory elevated TSH. The most common cause worldwide is iodine deficiency, while Hashimoto's thyroiditis is the most common cause in iodine-sufficient regions like the US.
Detail
Primary hypothyroidism results from an intrinsic defect in thyroid hormone production, distinguishing it from secondary (pituitary TSH deficiency) or tertiary (hypothalamic TRH deficiency) hypothyroidism. The negative feedback loop is intact, so low T3/T4 leads to loss of feedback inhibition on the pituitary, causing elevated TSH—the hallmark lab finding (high TSH, low free T4).
Etiologies include: Hashimoto's thyroiditis (autoimmune, anti-TPO and anti-thyroglobulin antibodies, most common cause in developed countries, associated with lymphocytic infiltration and germinal centers on histology); iodine deficiency (most common cause globally); iatrogenic (post-thyroidectomy, post-radioactive iodine ablation, external radiation); drug-induced (lithium, amiodarone, interferon-alpha); subacute (de Quervain) thyroiditis (transient); and congenital hypothyroidism (thyroid dysgenesis, dyshormonogenesis).
Clinical features reflect decreased metabolic rate: fatigue, cold intolerance, weight gain, constipation, bradycardia, dry skin, hair thinning, myxedema (non-pitting edema from glycosaminoglycan accumulation), menstrual irregularities, and delayed relaxation of deep tendon reflexes. Myxedema coma is a life-threatening severe manifestation with hypothermia, altered mental status, and hypoventilation, often precipitated by infection, cold exposure, or sedatives.
Lab findings: elevated TSH, decreased free T4, possible hyponatremia (SIADH-like), hyperlipidemia, elevated anti-TPO/anti-thyroglobulin antibodies in Hashimoto's.
Treatment is levothyroxine (synthetic T4) replacement, titrated based on TSH normalization. Monitor TSH every 6-8 weeks after dose changes until stable, then annually.
Key associations: Hashimoto's thyroiditis increases risk of other autoimmune conditions (T1DM, Addison's, pernicious anemia—polyglandular autoimmune syndromes) and slightly increases risk of thyroid lymphoma. Distinguish from subclinical hypothyroidism (high TSH, normal free T4) and sick euthyroid syndrome (low T3, variable T4/TSH in critically ill patients without primary thyroid pathology).
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- UpToDate: Hypothyroidism
- Pathoma: Endocrine Pathology
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.