ERM2 - Thyroid Pathology

• -Thyroid secretes thyroxine (T4) and Triiodothyronine (T3)
• -T4 (85%), T3 (15%)

• -T3 is the active hormone and binds nuclear receptors
• -most T3 comes from peripheral deiodination of T4
• -T4/T3 are mostly bound to TBG
• -T3 negatively regulates TSH

• -Iodine enters thyrocyte by NIS transporter
• -TPO organifies Thyroglobulin and iodine --> Tg bound to T3 and T4
• -thyroglobulin is stored in colloid
• -TSH binding triggers endocytosis of Tg and lysosomal proteolysis to release T3 and T4

• -low TSH
• -elevated T3/T4

Normal TSH (bellcurve shape: 0.3 to 4, median 1.5)

• -high TSH
• -low T3/T4

• -small change in T4 causes a large change in TSH
• -can pick up mild thyroid dysfunction with TSH

• 1. Elevated TBG
• -estrogens (OCPs, pregnancy)
• -acute hepatitis

• 2. Decreased TBG
• -androgens
• -glucocorticoids
• -liver failure
• -nephrotic syndrome

• Cold Intolerance (decreased heat production)
• Weight Gain (decreased appetite)
• Hypoactivity, lethargy, weakness
• Constipation
• Decreased reflexes
• Myxedemal (facial/periorbital)
• Dry cool skin
• Brittle Hair
• Bradycardia
• Dyspnea on exertion

-if hypothyroidism is severe and untreated then combined with an exacerbating medical condition symptoms can become serious

-exacerbation: trauma, infection, cold exposure, opiates

-clinical features: hypothermia, hyponatremia, bradycardia, hypotension, hypoglycemia

-50% mortality

• 1. Iodine deficiency (most common worldwide)
• 2. Congenital thyroid disorder
• 3. Thyroid tissue destruction
•      -Hashimoto's (autoimmune)
•      -Radiation
•      -Thyroidectomy
•      -Infiltrative diseases (very rare)
• 4. Drugs
•      -Li (bipolar)
•      -Amiodorone (Iodine containing)
•      -IFNa

• -most common cause in developing countries
• -fetal iodine deficiency (cretinism)
• -goiter (fetal hyperplasia)

• -autoantibodies against TPO, Tg and TSHR (blocking)
• -activated T cells cause thyrocyte apoptosis
• -can be goiterous or atrophic
• -more common in women (5:1)
• -precipitated by: infection, stress, sex steroids, pregnancy

• -occurance of hyper or hypo thyroidism during the post partum period
• -autoimmune (TPOab or TSI)
• -10% have permanent hypothyroidism
• -high risk: patients with hx of autoimmune disorder

• Clinical Course:
• 1. thymocytes are damaged (ie: due to infection) --> uncontrolled release of thyroid hormones
• 2. spike in T3/T4 inhibits TSH and Iodine uptake
• 3. over 6 wks hormones are degraded until there are low serum levels --> increased TSH
• 4. no hormone stores in thyroid to release, needs time to recover
• 

• -increased thyroid hormone in the circulation
• -most common cause: hyperthyroidism
• -determine cause by RAIU

• HIGH RAIU (hyperthyroidism)
• -autoimmine (Grave's)
• -toxic multinodular goiter
• -Toxic adenoma
• -hCG induced (choriocarcinoma, molar pregnancy)
• -TSH-secreting pituitary adenoma (rare)

• LOW RAIU (exogenous thyroid hormone)
• -iodine induced (increased hormone release)
• -thyroiditis

• -cardiac (tachy)
• -tremor
• -sweating
• -muscle wasting
• -prox muscle weakness
• -anxiety
• -goiter
• -increased appetite with wt loss
• -amenorrhea/oligomenorrhea

• -TSH R stimulating antibodies (TSI)
• -more common in women (9:1)
• -age 20-40

• Symptoms:
• -diffuse goiter with homogenous RAIU
• -exopthalmos (ab against orbital fibroblasts)
• -dermopathy (ab against skin)
• -thyroid acropachy (ab against bone)
• -pretibial myxedema

• -focal patches of hyperfunctioning follicular cells
• -independent of TSH
• -activating mutation in TSHR
• -rarely malignant

-can be treated with RAI (b/c rest of thyroid isn't taking up iodine so shouldn't be affected)

• 1. Diet (seaweed, kelp)
• 2. Contrast
• 3. Iodine solutions
• 4. topical antiseptics
• 5. Meds (amiodorone, expectorants)

• 1. Antithyroid drugs (methimazole, PTU)
• 2. Radioactive iodine
• 3. thyroidectomy

• 4. beta blockers
• 5. corticosteroids
• 6. Lithium
• 7. Potassium iodide

• -inhibit iodination (inhibit TPO)
• -PTU inhibits 5' deiodinase (inibits peripheral T4 to T3)
• -PTU is safe in first trimester by causes hepatotoxicity

• -used to tx toxic nodules or Grave's (autoabs still present but target is gone)
• -effective but slow response
• -80% develop hypothyroidism

• -reduces iodine binding and hormone release
• -many toxic side effects

• -blocks release of thyroid hormone (wolff chekoff effect)
• -used to get severe hyperthyroidism controlled quickly
• -loses effect quickly

• -common (clinically apparent in 4-7%)
• -up to 50% are incidentally discovered
• ->90% benign

• 1. Check TSH (if low --> RAIU)
• 2. RAIU
•      -hot nodules rarely malignant
•      -5-15% of cold nodules are malignant
• 3. FNA bx (cold nodules, >1cm)

• -ground glass nuclei with grooves
• -orphan annie eyes
• -good prognosis