ERM2 - Thyroid Pathology

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Author:
jknell
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184733
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ERM2 - Thyroid Pathology
Updated:
2012-11-20 21:29:05
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Endocrine Reproductive Pathology
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Endocrine and Reproductive Pathology
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  1. Hypothalamic-Pituitary-Thyroid Axis
  2. Hypothalamic-Pituitary-Thyroid Axis
    • -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
  3. Thyroid Hormone Synthesis
    • -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
  4. Hyperthyroid
    • -low TSH
    • -elevated T3/T4
  5. Euthyroid
    Normal TSH (bellcurve shape: 0.3 to 4, median 1.5)
  6. Hypothyroid
    • -high TSH
    • -low T3/T4
  7. Log-Linear Relationship bwtn T4 and TSH
    • -small change in T4 causes a large change in TSH
    • -can pick up mild thyroid dysfunction with TSH
  8. Causes of Alterations in TBG
    • 1. Elevated TBG
    • -estrogens (OCPs, pregnancy)
    • -acute hepatitis

    • 2. Decreased TBG
    • -androgens
    • -glucocorticoids
    • -liver failure
    • -nephrotic syndrome
  9. Hypothyroidism: Symptoms
    • 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
  10. Hypothyroidism: Myxedema Coma
    -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
  11. Primary Hypothyroidism: Causes
    • 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
  12. Hypothyroidism: Iodine Deficiency
    • -most common cause in developing countries
    • -fetal iodine deficiency (cretinism)
    • -goiter (fetal hyperplasia)
  13. Hypothyroidism: Hashimoto's
    • -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
  14. Post-Partum Thyroiditis
    • -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
  15. Thyrotoxicosis
    • -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
  16. Thyrotoxicosis: Symptoms
    • -cardiac (tachy)
    • -tremor
    • -sweating
    • -muscle wasting
    • -prox muscle weakness
    • -anxiety
    • -goiter
    • -increased appetite with wt loss
    • -amenorrhea/oligomenorrhea
  17. Grave's Disease
    • -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
  18. Toxic Multinodular Goiter (Plummer's Disease)
    • -focal patches of hyperfunctioning follicular cells
    • -independent of TSH
    • -activating mutation in TSHR
    • -rarely malignant
  19. Toxic Thyroid Adenoma
    -can be treated with RAI (b/c rest of thyroid isn't taking up iodine so shouldn't be affected)
  20. Iodine Induced Thyrotoxicosis: Iodine sources
    • 1. Diet (seaweed, kelp)
    • 2. Contrast
    • 3. Iodine solutions
    • 4. topical antiseptics
    • 5. Meds (amiodorone, expectorants)
  21. Hyperthyroidism: Treatment
    • 1. Antithyroid drugs (methimazole, PTU)
    • 2. Radioactive iodine
    • 3. thyroidectomy

    • 4. beta blockers
    • 5. corticosteroids
    • 6. Lithium
    • 7. Potassium iodide
  22. Methimazole and PTU
    • -inhibit iodination (inhibit TPO)
    • -PTU inhibits 5' deiodinase (inibits peripheral T4 to T3)
    • -PTU is safe in first trimester by causes hepatotoxicity
  23. Radioactive Iodine Treatment
    • -used to tx toxic nodules or Grave's (autoabs still present but target is gone)
    • -effective but slow response
    • -80% develop hypothyroidism
  24. Lithium
    • -reduces iodine binding and hormone release
    • -many toxic side effects
  25. Potassium Iodide
    • -blocks release of thyroid hormone (wolff chekoff effect)
    • -used to get severe hyperthyroidism controlled quickly
    • -loses effect quickly
  26. Thyroid Nodules: Incidence
    • -common (clinically apparent in 4-7%)
    • -up to 50% are incidentally discovered
    • ->90% benign
  27. Thyroid Nodules: Workup
    • 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)
  28. Papillary Thyroid Cancer
    • -ground glass nuclei with grooves
    • -orphan annie eyes
    • -good prognosis

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