Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to 11 26 noon conference ac
Similar to 11 26 noon conference ac (20)
More from Virginia Mason Internal Medicine Residency
More from Virginia Mason Internal Medicine Residency (20)
Recently uploaded
Recently uploaded (20)
11 26 noon conference ac
- 2. © 2016 Virginia Mason Medical Center 2 Objectives Chronic Autoimmune Thyroiditis (Hashimoto’s Thyroiditis) • Epidemiology • Pathophysiology • Clinical Presentation • Diagnosis • Treatment • Review illness script
- 3. © 2016 Virginia Mason Medical Center Epidemiology 3 • Most common cause of hypothyroidism in US • Prevalence: 0.1-2% • 6-8 times more likely in women • Age 30-50 • Incidence increases with age in men • linked to other autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, pernicious anemia, diabetes mellitus and Sjögren's syndrome.
- 4. © 2016 Virginia Mason Medical Center Pathophysiology 4 • Autoimmune-mediated destruction of the thyroid gland involving apoptosis of thyroid epithelial cells • Autoantibodies toward: • Thyroglobulin • Thyroid peroxidase • TSH-R • Common pathologic feature: lymphocytic infiltration and follicular destruction • Precipitating factors: • Genetic susceptibility • Thyroid injury • Infection • Radiation, drugs, stress • Excessive Iodine
- 5. © 2016 Virginia Mason Medical Center Question 1 Which physical exam finding is most sensitive in the diagnosis of hypothyroidism? A. Slow Movements B. Pretibial Edema C. Puffiness of face D.Corse skin 5
- 6. © 2016 Virginia Mason Medical Center Question 1 Which physical exam finding is most sensitive in the diagnosis of hypothyroidism? A. Slow Movements B. Pretibial Edema C. Puffiness of face D.Corse skin 6
- 7. © 2016 Virginia Mason Medical Center 7
- 8. © 2016 Virginia Mason Medical Center Clinical Presentation 8 • Slow gradual loss of thyroid function (months to years) and diffuse painless goiter • Usually subclinical hypothyroidism • Elevated TSH on routine screening • Can present early with transient period of hyperthyroidism (less common)
- 9. © 2016 Virginia Mason Medical Center 9
- 10. © 2016 Virginia Mason Medical Center Diagnosis • Diffuse swelling of the thyroid gland without any other cause • High levels of anti-TPO and/or anti-TG • Primary hypothyroidism w/o any other cause • Histological diagnosis infrequently done 10
- 11. © 2016 Virginia Mason Medical Center 11
- 12. © 2016 Virginia Mason Medical Center 12
- 13. © 2016 Virginia Mason Medical Center 13
- 14. © 2016 Virginia Mason Medical Center Question 2 32 yo G3P2 at 10 weeks gestation with mild nausea, TSH of 0.1 (0.5-5), T4 of 14 (4-12). Next step? A. Measure free T4 B. Reassurance C. Start propylthiouracil D.Thyroid Ultrasound E. Measure T3 14
- 15. © 2016 Virginia Mason Medical Center Question 2 32 yo G3P2 at 10 weeks gestation with mild nausea, VS WNL, TSH of 0.1 (0.5-5), T4 of 14 (4-12). Next step? A. Measure free T4 B. Reassurance C. Start propylthiouracil D. Thyroid Ultrasound E. Measure T3 15 During pregnancy, estrogen increases TBG=increase bound T4 = inc free T4 AND B-HCG directly stimulates TSH-R feedback downreg of TSH Pregnancy TSH Ref Range: - 1st Tri: 0.1-2.5 - 2nd Tri: 0.2-3.0 - 3rd Tri: 0.3 – 3.0
- 16. © 2016 Virginia Mason Medical Center 16 Treatment • Most patients do not require treatment • Small goiter, asymptomatic • Thyroid replacement for symptomatic goiter and/or hypothyroidism (1 ug L-T4/lb/day) • Unclear if subclinical hypothyroidism should be treated*
- 17. © 2016 Virginia Mason Medical Center 17
- 18. © 2016 Virginia Mason Medical Center Other treatment options • Glucocorticoids, surgery • Painful, obstructive goiter • Chloroquine, selenium, xray therapy • Not recommended, poor evidence 18
- 19. © 2016 Virginia Mason Medical Center Illness Scripts 19 Chronic Autoimmune Thyroiditis (Hashimoto’s Thyroiditis) Painless thyroiditis (silent thyroiditis or lymphocytic thyroiditis) Pathophysiology Anti-TPO and/or Anti-TG Anti-TPO and/or Anti-TG (excess iodine, cytokine release) Epidemiology 30-50 yo F>M 30-50yo F>M Time course chronic Acute and subacute Clinical presentation usually asymptomatic, firm, irregular, nontender goiter acute symptoms of hyperthyroidism, followed by hypothyroidism, small painless goiter is present in 50 percent of patients Diagnostics Labs: High TSH, normal elevated T4 Serologic testing: Anti-TPO and/or Anti-TG Labs: Low TSH, high T4 Serologic testing: Anti-TPO and/or Anti-TG (less high than Hashimoto’s) Therapeutics Thyroid replacement BB, GC: hyperthyroid phase Thyroid replacement for: hypothyroid phase
Editor's Notes
- Title your presentation “Noon Conference” Prevents inadvertently giving away the case.
- Pregnancy — During pregnancy, there is a marked increase in CD4+CD25+ regulatory T cells which lead to diminished function of both T cells and B cells [77], and the rebound from this immunosuppression is thought to contribute to the development of postpartum Hashimoto's thyroiditis. Pregnancy-associated immune suppression is associated with a shift to Th2 T cells and a shift in cytokine profiles [78]. A variety of local factors at the immune cell-trophoblast interface are also known to be important modulators of immune function in pregnancy. The trophoblast cells, located in the placenta and subject to maternal immune surveillance, serve as physical barriers between mother and fetus, and they have been shown to express several immune-modulating molecules, such as human leukocyte antigen-G (HLA-G), Fas ligand, and indoleamine 2,3-dioxygenase as well as secreting a variety of cytokines. HLA-G is one of the members of the MHC class I family and is known to inhibit natural killer function and dendritic cell maturation. Fas ligand interacts with Fas antigen and induces apoptotic cell death of fetal antigen-reactive maternal lymphocytes. Indoleamine 2,3-dioxygenase, which catalyzes tryptophane in lymphocytes, has proven to be critical in the maintenance of allogeneic pregnancy in the mouse. Other than these local modulators, progesterone produced by the placenta affects cytokine profiles across the whole maternal immune system [79,80]. Approximately 20 percent of patients with postpartum thyroiditis go on to develop classical Hashimoto's disease in later years [81]. Iodine intake — Mild iodine deficiency is associated with a lower prevalence of Hashimoto's disease and hypothyroidism, while excessive intake is associated with a higher prevalence. As an example, in China, autoimmune thyroiditis was found in 0.3 percent of those with mildly deficient iodine intake and 1.3 percent of those with excessive iodine intake [82]. Similarly, high iodine-containing drugs, such as amiodarone, often precipitate autoimmune thyroiditis, although a variety of mechanisms have been suggested. (See "Amiodarone and thyroid dysfunction".) Radiation exposure — Environmental radiation exposure may increase the possibility of developing markers of autoimmune thyroid disease, although the evidence for this and developing hypothyroidism are conflicting [83-88]. Following the tragic Chernobyl nuclear accident, the exposed children developed a high frequency of thyroid autoantibodies [89]. In addition, 12 to 15 years after the Chernobyl accident, thyroid peroxidase (TPO) antibodies were elevated with a dose-response relationship in a cohort of radiation-exposed individuals [87]. In the same cohort, a small increase in subclinical hypothyroidism related to the level of radiation exposure was found [90]. However, the risk of subclinical hypothyroidism was less when TPO antibodies were present. In another study in the Chernobyl region comparing people with high and low exposure levels, the prevalence of TPO antibodies increased and then abated without evidence of appreciable levels of hypothyroidism [91]. In a population-based study of 4299 subjects, 160 had an occupational exposure to ionizing radiation [86]. Nearly 60 percent of the subjects worked in a nuclear power plant, while the rest were either medical or laboratory workers. Ten percent of the female subjects with radiation exposure met criteria for autoimmune thyroid disease (anti-TPO antibodies greater than 200 international units/mL and hypoechogenicity on ultrasound) compared with 3.4 percent of those without an exposure. Subjects with greater than five years of exposure to ionizing radiation were at particularly high risk. However, in the long-term follow-up of atomic bomb survivors, no dose-response relationship was found for autoimmune thyroid disease, the strongest evidence so far that no association exists [83]. Similarly, the long-term follow-up of people exposed by the releases from the Hanford nuclear facility found no increase in autoimmune thyroid disease and hypothyroidism [84]. Fetal microchimerism — Fetal cells have been identified within maternal thyroid glands in patients with autoimmune thyroid. Such cells may initiate graft versus host reactions within the thyroid gland and play a significant role in the development of Hashimoto's thyroiditis [38,92-95]. To date, however, this remains hypothetical.
- TPOAb, and less frequently TGAb are present in serum. High levels are diagnostic of autoimmune thyroid disease. TGAb are positive in about 80% of patients, and if both TGAb and TPOAb are measured, 97% are positive. Many thyroid experts check serum TPO antibodies in such patients to confirm the diagnosis of Hashimoto's, especially if the diagnosis is not evident based on a strong family history of autoimmune thyroid disease or a typical examination (a slightly firm, rubbery, symmetrical gland, possibly with a palpable pyramidal lobe).
- Free T4 unreilaible low in in pregnancy due to artifact Patient is euthyroid without overt hyperthyroidism and asymptomatic, no tx indicated Normal thyroid examination
- painless thyroiditis include excess iodine intake and various cytokines. A syndrome very similar to this disorder can occur in patients treated with interferon alfa, interleukin-2, lithium, tyrosine kinase inhibitors, as well as cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and immune checkpoint inhibitors. These observations raise the possibility that cytokines released in response to some (subclinical) injury or infection might initiate the disorder.