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Authors: Arthur S. Tischler, M.D., Anastassios G. Pittas, M.D.
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1. Case 1 Answers – Hypothyroidism due to Hashimoto’s

  1. Answer B. To learn that TSH is the most specific and most sensitive test for evaluation of thyroid function. However, in this case measurement of TSH alone may not be enough, as she may have secondary hypothyroidism from Sheehan's syndrome. A "normal" TSH does not rule out secondary causes of hypothyroidism. Thyroid antibodies are generally not done initially, but if primary hypothyroidism is suggested on the basis of an elevated TSH, then thyroid antibodies will highly suggest autoimmune cause (Hashimoto's).
  2. Answer A. To learn that an elevated TSH suggests primary hypothyroidism. The most common causes of primary hypothyroidism are autoimmune (Hashimoto's), subacute thyroiditis and post-partum thyroiditis. Given her high antibody titer, she probably has Hashimoto's.
  3. Answer A. Hypothyroidism in women results in changes in the menstrual cycle. Women complain of menorrhagia but can become anovulatory. Hypothyroidism through the feedback loop on the hypothalamus results in increased secretion of TRH which can increase prolactin levels. Elevated prolactin has a direct inhibitory effect on gonadotropin secretion which reduces secretion of LH/FSH and causes amenorrhea.
  4. Possibly. The most common cause of hypothyroidism in adults is Hashimoto's thyroiditis. Given positive antibodies, she probably has Hashimoto’s which requires lifelong therapy. It is important to distinguish from the hypothyroid phase of subacute thyroiditis which improves over time and does not require life-long therapy.
  5. PATH - Hashimoto's thyroiditis is typically a diffuse process characterized by numerous lymphocytes, germinal centers and plasma cells interspersed between follicles, and transformation of follicular epithelium into Hurthle cells. Hurthle cells are large, polygonal cells with granular eosinophilic cytoplasm and hyperchromatic nuclei with prominent nucleoli.
  6. PATH - Typical FNA would show Hurthle cells (that often have a "syncytial-like" appearance in this disease) admixed with a mixed population of mononuclear inflammatory cells.
  7. PATH - Hashimoto's may mimic Hurthle cell adenomas or carcinomas in atypical cases with asymmetrical involvement of the thyroid, minimal clinical findings or FNA sampling that shows disproportionate representation of Hurthle cells without the accompanying inflammation. The correct diagnosis is usually apparent in histologic study of a thyroid resection specimen because Hurthle cell neoplasms are usually solitary and encapsulated. Capsular invasion distinguishes carcinoma from adenoma.

2. Case 2 Answers – Follicular Adenoma

  1. Answer A. She is hyperthyroid based on her thyroid function results. Her plasma total T4 and T3 are elevated with a suppressed TSH, indicating excess thyroid hormone most likely secreted from the thyroid; however, exogenous administration of thyroid hormone would appear the same biochemically.
  2. Graves, toxic MNG, Toxic Adenoma and Subacute Thyroiditis are the most common causes of hyperthyroidism.
  3. Answer B. False. Lid lag is caused by the synergism between excess thyroid hormone and the adrenergic sympathetic nervous system on a smooth muscle called the Müller muscle in the superior palpebral muscle. When activated, this muscle interferes with lid closure resulting in a "lag" in the lid compared to the globe as the patient looks down. Activation by excess thyroid hormone from any source or by the sympathetic nervous system when a person is "scared" will result in lid lag. She does not have Graves and is therefore not at risk for developing thyroid eye disease which includes periorbital edema, proptosis (protrusion forward), chemosis (conjunctival edema) or injection (increase perfusion secondary to irritation).
  4. Answer C. Multinodular goiter given the examination and negative antibodies. Thyroid scan and uptake will differentiate between the most common causes of hyperthyroidism.
  5. I-123 thyroid uptake and scan is the most useful test in determining the etiology of hyperthyroidism. The different types of scans/uptakes will be discussed in class.
  6. PATH - Follicular adenoma vs. follicular carcinoma.
  7. PATH - Adenomatous nodules are usually multiple and are composed of varying sizes follicles. Generally there is no evidence of compression of the adjacent thyroid parenchyma. The capsules of adenomatous nodules are usually incomplete.
  8. PATHAnswer A.. Extensive sampling of the capsule. Follicular carcinomas, by definition, show evidence of capsular and/or vascular invasion.
  9. PATH - Follicular adenomas are benign lesions.

3. Case 3 Answers – Metastatic Papillary Thyroid Carcinoma

  1. Answer A (or B). You first need to determine whether this nodule is functional, which is easily done with measurement of TSH. Functional nodules (suggested by a very low TSH or by appearing ‘hot’ on scans) are almost never cancerous; therefore, biopsy is not needed. Over 90% of thyroid nodules are non-functional. Imaging studies are not usually recommended in a patient with a solitary nodule who is clinically and biochemically euthyroid, as most nodules will appear "cold" or "cool" on these scans.
  2. PATH - Answer B. This is metastatic papillary thyroid cancer involving a lymph node.
  3. PATH - Discuss characteristics of papillary thyroid carcinoma. Define papilla (Greek = “nipple”), discuss psammoma bodies, Orphan Annie eye nuclei, follicular variant of PTC.
  4. PATH - Exposure to radiation is the most significant risk factor for development of thyroid cancer. There is an excess risk of developing thyroid cancer even greater than 30 years after head and neck radiation. Radiation during childhood increases the risk more. There has been a large increase in papillary thyroid cancers in children following the nuclear accident in Chernobyl. However, most people with thyroid cancer have not been exposed to radiation.
  5. PATH - Answer B. Most papillary thyroid cancers have an indolent course. The 20 year mortality for papillary thyroid cancer is 5%. If the patient is younger than 40 and has a small encapsulated tumor without local or distant spread, the 20 year mortality is 1%. Poor prognostic factors include age >40, distant metastatic disease, local invasion (not adenopathy) into muscle/perithyroidal tissue, large size (especially >4 cm). Her recurrence rate is 20-30% without additional treatment with radioactive iodine.

4. Case 4 Answers – Medullary Thyroid Carcinoma

  1. PATH - A neoplasm composed of round to polyhedral cells without evidence of the formation of follicles or papillae.
  2. PATH - Amyloid, most likely derived from calcitonin or a calcitonin precursor.
  3. PATH - Answer C. Chromogranin is a generic neuroendocrine marker that distinguishes the tumor from tumors of thyroid follicular epithelium. Calcitonin, the specific product of C-cells, establishes the diagnosis of medullary thyroid carcinoma.
  4. PATH - The tumor is derived from C-cells.
  5. Some MTC (approximately 20%) are inherited as autosomal dominant traits in association with MEN Type 2A or 2B syndromes. Rarely, MTC may be inherited without associations with MEN.
  6. Dominant activating germ line mutations of different regions of the RET proto-oncogene are responsible for the development of MEN 2A or 2B and familial (isolated) MTC. Somatic RET mutations occur in small percentages of sporadic tumors of these types.