USMLE Step 1 Review/Endocrine

Hypothalamic-pituitary-thyroid axis

 * Hypothalamus → thyrotropin releasing hormone (TRH)
 * Pituitary → thyroid stimulating hormone (TSH)
 * Thyroid → T3, T4

Thyroid hormone synthesis

 * 1) Plasma iodide enters thyroid follicular cells via sodium iodine (NaI) cotransporter via secondary active transport.
 * 2) Within the cell, thyroperoxidase (TPO) oxidizes iodide to either atomic iodine (I) or iodinium (I+).
 * 3) Oxidized iodine species bind tyrosine residues of thyroglobulin, the major protein of thyroid colloid.
 * 4) * Tyrosine + a single iodine atom: monoiodotyrosine (MIT)
 * 5) * Tyrosine + two iodine atoms: diiodotyrosine (DIT)
 * 6) MIT and DIT combine:
 * 7) * MIT + DIT: triiodothyronine (T3)
 * 8) * DIT + DIT: tetraiodothyronine (T4, also called thyroxine)
 * 9) * DIT + MIT: reverse T3 (rT3, which is biologically inactive)
 * 10) Proteases digest release thyroglobulin, releasing the active hormones T3 and T4 into the bloodstream.
 * 11) Peripherally, 5'-deiodinase converts T4 to the more active T3.

Antithyroid drugs
Compete with iodide for the NaI cotransporter in thyroid follicular cells:
 * Perchlorate
 * Thiocyanate
 * Goitrin

Inhibit thyroperoxidase:
 * Propylthiouracil (also inhibits 5'-deiodinase)
 * Methimazole

Inhibit 5'-deiodinase:
 * Propylthiouracil (also inhibits thyroperoxidase)

Pathology

 * Hashimoto's thyroiditis: Most common cause of primary hypothyroidism in the US, F > M. Autoimmune, demonstrating lymphocytic infiltration microscopically. Associated with HLA-DR5. Clinical course may begin with hyperthyroidism resulting from thyroid destruction and release of thyroid hormone; ultimately results in hypothyroidism (fatigue, cold intolerance, weight gain, constipation, fragile hair, dry skin). Treated with hormone replacement (T4, levothyroxine).


 * Graves' disease: Most common cause of hyperthyroidism in US, F > M. Autoimmune, resulting from autoantibody stimulating the TSH receptor on thyroid follicular cells. Results in hyperthyroidism (heat intolerance, tachycardia, weight loss, diarrhea, hair/skin changes), frequently a diffuse goiter, and characteristic pretibial myxedema, retroorbital fibrosis, and exophthalmos. Treated with antithyroid drugs (propylthiouracil, methimazole, radioactive iodine). Exophthalmos is irreversible despite treatment.

Thyroid cancer

 * 1) Papillary thyroid carcinoma: Most common (75%), Orphan-Annie nuclei, psammoma bodies.
 * 2) Follicular thyroid carcinoma:
 * 3) Medullary thyroid carcinoma: Neoplastic parafollicular cells (C-cells), ↑calcitonin, derived embryologically from ultimobranchial body, associated with mutations in RET gene (same as in MEN type 2).
 * 4) Anaplastic thyroid carcinoma: Rare, poor prognosis.

Multiple endocrine neoplasia
All autosomal dominant. Consider MEN when there is a strong family history of medullary thyroid carcinoma.