Pathology March 30, 2001 11:00
Dr. Mira
Joseph Cordova/ Jody Haigood
Dr. Mira did not go for the full hour.
Endocrine CPC
Exopthalmos is probably cause by autoimmune actions. This is why other forms of hyperthyroidism do not cause exopthalmos, only Grave’s.
Case #3 on Robbins Disk:
A 38 year old attorney reported for her yearly physical examination complaining of tiredness, difficulty concentrating on her work, and a noticeable decline in her memory over the past several months. She attributed many of her symptoms to the stress load of work. She reveals that frequency of her bowel movements had decreased from once daily, six months ago, to once every two to three days. She had difficulty avoiding a gain in weight and despite warm weather, she felt chilled without a light sweater. Her only medication was an oral contraceptive.
PE revealed a well-proportioned woman with sparse eyebrows. Also showed a diffusely moderately enlarged thyroid gland with a prominent pyramidal lobe above the isthmus (This is not necessarily abnormal).
Her lab values:Normal:
T4 total: 5.5ug/dL (5-11.5)
T4 Free: 0.25ng/dL (0.76-1.8)
TSH: 22.0 uU/mL (0.4-4.5)
Anti-thyroglobulin antibodies: positive, 1:640 (Negative)
Antimicrosomal antibodies: positive, 1:5120 (Negative)
The last two values tell you that she has an autoimmune disease with thyroid manifestations (hypothyroidism). This gives you a diagnosis of Hashimoto’s Thyroiditis. It is not Grave’s disease because Grave’s is an autoimmune disease with hyperthyroidism.
Fine Needle Aspiration reveals lymphocytes, plasma cells, and cohesive clusters of enlarged follicular cells with abundant eosinophilic granular cytoplasm and nucleoli (Hurthle cell).
- Her TSH is very high and her T4 is really low. What is wrong with her? Primary hypothyroidism.
These two values tell you that the pituitary gland is sending out a lot of stimulating hormone because the titer is not working hard enough.
- 80% of patients will have anti-thyroglobulin antibodies.
Slides of Hashimoto’s Thyroiditis
Gross picture: fleshy, soft, pale lobular nodules protrude above the cut surface of the gland. The nodules can be irregular in appearance. The depressed areas in between the nodules are due to fibrosis. Grossly it looks deep red and nodular (with Grave’s disease it is diffuse). See more fibrous components in Hashimoto’s.
Q: Can Hashimoto’s give you hyperthyroidism? Yes
Q: What do you think a radioactive scan will look like on this patient? The distribution of iodine will not be homogenous because some parts are functional and others are not; overall there will be decreased uptake because the glands are hypoactive.
Low power: Thyroid parenchyma is replaced by a dense lymphocytic infiltrate that includes lymphoid follicles with germinal centers. Thyroid follicles are generally small, may undergo atrophy, with metaplasia of solid epithelial clusters into Hurthle cells. Interstitial fibrosis may also be present. Basically you see lymphoid follicles, patches of thyroid follicles, and fibrosis.
Q: What other thyroid diseases show lymphocytic infiltrate? Grave’s disease, chronic thyroiditis, granulomatous thyroiditis, Riedel’s thyroiditis
High power: Hurthle Cells, Germinal Centers of lymphoid follicles, and more lymphocytes are diagnostic of Hashimoto’s. You see Hurthle cells as enlarged cytoplasm containing eosinophilic granules with nuclear enlargement and some atypia. These cells are found in between the germinal centers and thyroid follicles within the cytoplasm.
Q: Patients with Hashimoto’s may have circulating antithyroid autoantibodies; what two processes contribute to formation these antibodies? 1) Autoimmune process – lymphocytes make antibodies against the TSH receptors 2) Destruction of follicles with exposure of antigens usually hidden, may incite an immune response leading to formation of antithyroid peroxidase and antithyroglobulin antibodies.
Q: What is the result of progression of Hashimoto’s to its endstage? Hypothyroidism with destruction of follicles and fibrous replacement of the gland.
Q: In this case, how can one explain the total T4 within reference range in spite of hypothyroidism? (He read this verbatim from the CD)- The TSH is the most sensitive and reliable test for thyroid function. It exquisitely measures the response of the pituitary to ambient thyroxine. In fact, each person’s free T4 and total T4 generally are maintained within narrow limits compared to the reference range for the entire population. For this reason, the TSH is far more sensitive and responds in logarithmic fashion to small deviations of T4. Also remember that the total T4 reflects the majority bound to proteins, as well as the small amount of active free T4. Birth control pills are one of many substances that can increase the quantity of binding proteins and drive up the level of total T4 without changing the free fraction.
Myxedema Clinical picture: Initial symptoms are fatigue, lethargy, cold intolerance, and general listlessness and apathy, with slowing of speech and intellectual function. Other findings with the generally slowed metabolism include decreased sweating, constipation, slow motor function, and dilatation of cardiac chambers with poorly functioning myocytes (hypothyroid cardiomyopathy). With chronic myxedema, there is periorbital edema, thickened dry coarse skin with thickening of facial features, and tongue enlargement.
Q: What are the causes and clinical features of congenital hypothyroidism? Causes include iodine deficiency during pregnancy, inborn errors of metabolism, antithyroid therapy during pregnancy. Clinically there is retardation of physical and mental growth. The changes usually do not manifest until weeks to months after birth, at which time changes are largely irreversible.
End stage chronic thyroiditis: You can see how a patient would have hypothyroidism. Thyroid is more pale and atrophic, replacement of parenchymal tissue with fibrous tissue.
Q: What is another potential long-term thyroid complication of irradiation to the neck? Papillary thyroid carcinoma
Atrophy and Fibrosis – low power: There is only a little bit of thyroid tissue left
Q: What treatment is indicated in end stage Hashimoto's thyroiditis or other forms of hypothyroidism? Thyroid hormone replacement