# USMLE Step 1 Review/Endocrine
## Thyroid
### Hypothalamic-pituitary-thyroid axis

* 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.

### Pharmacology
#### 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

* Papillary thyroid carcinoma
* Papillary renal cell carcinoma
* Serous papillary ovarian adenocarcinoma
* Endometrial adenocarcinomas (papillary serous carcinoma)
* Meningioma
* Mesothelioma
* 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

* Marfan's syndrome
* MEN type 2b
* Homocystinuria
* Ehlers-Danlos syndrome
All autosomal dominant. Consider MEN when there is a strong family history of medullary thyroid carcinoma.
| Type | Notes | Gene |
| 1 (Wermer syndrome) | 3 Ps Pituitary adenoma (eg, prolactinoma) Parathyroid hyperplasia Pancreatic tumors (eg, insulinoma) | MEN1, chromosome 11 |
| 2a (Sipple syndrome) | Medullary carcinoma of the thyroid Pheochromocytoma Hyperparathyroidism | RET, chromosome 10 |
| 2b (previously type 3) | Medullary carcinoma of the thyroid Pheochromocytoma Mucosal neuromas Marfanoid body habitus | RET, chromosome 10 |

## External links

* Memorable Medicine: Free Learning Resources and Forums