USMLE Step 1 Review/Endocrine
- Hypothalamus → thyrotropin releasing hormone (TRH)
- Pituitary → thyroid stimulating hormone (TSH)
- Thyroid → T3, T4
Thyroid hormone synthesis
- Plasma iodide enters thyroid follicular cells via sodium iodine (NaI) cotransporter via secondary active transport.
- Within the cell, thyroperoxidase (TPO) oxidizes iodide to either atomic iodine (I) or iodinium (I+).
- Oxidized iodine species bind tyrosine residues of thyroglobulin, the major protein of thyroid colloid.
- Tyrosine + a single iodine atom: monoiodotyrosine (MIT)
- Tyrosine + two iodine atoms: diiodotyrosine (DIT)
- MIT and DIT combine:
- MIT + DIT: triiodothyronine (T3)
- DIT + DIT: tetraiodothyronine (T4, also called thyroxine)
- DIT + MIT: reverse T3 (rT3, which is biologically inactive)
- Proteases digest release thyroglobulin, releasing the active hormones T3 and T4 into the bloodstream.
- Peripherally, 5'-deiodinase converts T4 to the more active T3.
Compete with iodide for the NaI cotransporter in thyroid follicular cells:
- Propylthiouracil (also inhibits 5'-deiodinase)
- Propylthiouracil (also inhibits thyroperoxidase)
- 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.
- Papillary thyroid carcinoma: Most common (75%), Orphan-Annie nuclei, psammoma bodies.
- Follicular thyroid carcinoma:
- 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).
- 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.
|1 (Wermer syndrome)||3 Ps
||MEN1, chromosome 11|
|2a (Sipple syndrome)||
||RET, chromosome 10|
|2b (previously type 3)||
||RET, chromosome 10|